ALBERT

Notes: Five human teratoma cell lines have been characterized for the presence of a certain number of marker antigens whose presence or absence has been shown to be characteristic of mouse embryonal carcinoma (EC) cells. Four out of the five lines have been shown to respond to at least some of the criteria associated with murine EC cells even though only limited in vitro differentiation could be demonstrated. The significance of certain unusual marker antigen combinations present on the cell line Tera I and its clones and so far unobserved for the murine model is discussed. The observation in Tera I populations of cells carrying simultaneously both the F9 and β2-microglobulin or HLA antigens, suggest that the human cell lines may represent a novel material for the study of mammalian differentiation.

Notes: Principles of Gene Manipulation. Studies in Microbiology

Notes: A healthy 22-year-old woman was noted to have erythrocytes of the Pk phenotype: a strong Pk antigen, no detectable P antigen and anti-P antibody in her serum. Her erythrocytes contained four to six times as much Pk glycolipid (globotriaosylceramide or CTH) and approximately half as much P glycolipid (globotertraosylceramide or globoside) as normal red cells. The structures of CTH and globoside were characterized by analysis of permethylated sugars and complement fixation in addition to chromaographic mobility and sugar composition. Inasmuch as the erythrocytes of two Pk individuals that were analysed previously (Marcus et al., 1976) contained no detectable globoside, these abnormalities appear o represent a new phenotype in the P blood group system.

Notes: We studied 201 unrelated French Basque individuals for HLA and Bf polymorphisms. The haplotypes of eighty-seven of them were deduced from family studies. The results show the frequency of the Bf F1 allele (0.1393) which is the highest one currently reported. They confirm the high frequencies of HLA-Aw19.2 and B18 previously reported in that population and show that a whole haplotype with strong linkage disequilibria, namely Aw19.2, Cw5, B18, Bf F1, DRw3 is frequent. On the other hand, the gene frequency of Bf S is decreased (0.5497) as compared with the other European Caucasoïd populations, while a slight increase in the Bf F gene frequency (0.2960) appears. These results point out that it is of importance to consider the genetic background in choosing the population where linkage disequilibria are to be studied.

Notes: The genetic control of hybrid resistance to BALB/c fibrosarcoma Meth-A was investigated. A Meth-A tumour grew slower in (BALB/c X C57BL/6)F1 and reciprocal hybrid mice than in syngeneic BALB/c mice and was also found to grow slower in females than in males. Significant F1 resistance was demonstrated after both subcutaneous and intraperitoneal injection of tumour cells. However, (BALB/c X DBA/2)F1 mice did not show any significant resistance to Meth-A. In H-2 linkage studies of [BALB/c X (BALB/c X C57BL/6)] backcross mice, no statistically significant differences in the resistance of H-2 heterozygotes and homozygotes to Meth-A were observed. These results indicated that F1 hybrid resistance to Meth-A was controlled by non-H-2-linked resistance factor(s). No linkage was observed between resistance to Meth-A and coat colour c- and b-loci.

Notes: CBA/N mice have an X-linked B cell defect which prevents them from responding to non-mitogenic thymic independent (TI-II) antigens such as dinitrophenylated (DNP-AGG) Ficoll. The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-AGG-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a ‘rescue'; they mounted strong plaque-foriming cell 7 days after in vitro exposure to DNP-AGG-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells could bind significant quantities of DNP-AGG-Ficoll, however, after, in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-AGG-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-AGG-Ficoll to the ‘rescuing’ F1 female cells.Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse μ serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP-AGG hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.

Notes: Results of a population study with all currently available B-cell specific alloantisera indicate that eight antigens controlled by the RhLA-linked DR locus can now be identified. This leaves a gene frequency of about 0.15 for unidentified or ‘blank’ antigens of that locus. Of the nine identifiable la antigens which are not controlled by the DR locus, three or four may form the basis of a second series which is probably also controlled by the RhLA region.

Notes: Induction of tolerance to bovine serum albumin was studied in mice selected for high (H) or low (L) antibody responsiveness and in their F1 hybrids. No high or low zone tolerances were obtained in H mice whereas L mice were susceptible to tolerance induction by the two schedules. H mice were immunized by repeated injections of tolerogenic BSA for low zone tolerance induction but not after the administration of a single high dose of tolerogenic BSA. Resistance to tolerance induction is dominant in F1 hybrids.

Notes: An attempt is made to account for immunoglobulin chain synthesis in terms of genetic events involving IS or controlling elements analogous to those found in bacteria, maize and drosophila. Transposition of variable and constant genes and normal immunoglobulin chain synthesis as well as qualitative and quantitative abnormalities might be explained by such regulatory elements. Intrachromosomal transpositions over short distances would be expressed as apparent hypermutability or redundancy of the variable DNA segment. The constant gene might comprise four sequences coding for the three homology domains and the hinge, separated by intervening sequences. A strong preference for shortrange transposition on the same chromosome and immobilization of the controlling element in the end might account for allelic exclusion.

Notes: Fab2 fragments from antisera raised in rabbits with partially purified cellular and serum HLA antigens were tested for their ability to block the cytolytic activity of operationally specific HLA-A, B alloantisera. One Fab2 fragment preparation blocked the cytolytic activity of all the HLA-A,B alloantisera tested; the remaining nine inhibited the lytic activity of alloantisera to certain HLA-A,B allospecificities, suggesting that these xenoantisera contain antibody to certain HLA-A,B allotype determinants or to closely associated structures. In contrast to previous reports in the literature none of the xenoantisera contained significant amounts of antibodies to human β2-microglobulin.

Notes: Serum IgG (7S) levels differed significantly for chickens from 10 different inbred lines. Within lines differences between B blood groups were statistically significant.The genetic control of serum IgG was further examined using birds from B complex haplotypes marked at the B locus and the Ir-GAT locus. Birds from each of five subgroup haplotypes (B1B1Ir-GAT-Lo and -Hi, B19B19Ir-GAT-Lo and -Hi, and B2B2Ir-GAT intermediate) were tested for levels of serum IgG at 3, 6, 9, and 21 weeks of age. The rate and level of IgG reached in the serum was more than two-fold greater in the GAT-Hi birds than in the GAT-Lo. The Ir region of the B complex exerts some control over the ontogenesis of IgG, though most of the genetic variation seems not to be B complex associated.

Notes: Dorso-ventral vaginal septa were observed in congenic mouse strains. Strain C57BL/10Sn, H-2b, had the highest frequency, 22%; B10.A/SgSn, H-2a, had the lowest frequency, 4%, P 〈0.001. The frequency was about 17% in the F1, females. Septa were found in 16% and 15% of the B10.D2/nSn and B10.BR/SgSn strains, respectively, indicating that at least two loci within the H-2 complex influence its frequency.

Notes: The phylogenetic distribution of antigens present on human lymphocytes was investigated by incubating human or simian cells with murine anti-human monoclonal antibodies and then determining the level of reactivity with a radiolabelled anti-murine IgG reagent. The monoclonal antibodies used were specific for a T-cell antigen, lymphoid and lymphoid:myeloid antigens, Ia antigens, and β2 microglobulin. The cells examined included B- and T-lymphoblastoid cell lines and fresh peripheral blood lymphocytes separated by sheep erythrocyte rosetting into T-cell and non T-cell fractions. Results of these studies showed that the antibodies gave complete cross-reactivity with gorilla and chimpanzee cells while B-cell lines of orangutan origin had lost lymphoid and β2 microglobulin markers. Gibbon cells and cells of Old World and New World monkeys reacted strongly only with monoclonal antibodies against Ia antigenic determinants. These Ia antigens were found on the non T-cell fraction of fresh peripheral lymphocytes, on B-cell lines and on some virus induced T-cell tumour lines. Immunoprecipitation analysis using the anti-Ia antibodies showed a degree of molecular diversity on owl monkey and marmoset cells compared to the Ia antigens associated with human cells.

Notes: C3H/HeN x NZB/BIN F1 mice were primed and challenged with DNP-Ficoll, a thymic independent (TI-2) antigen. They developed strong IgM and IgG carrier-specific memory responses: DNP-pneumococcal polysaccharide or DNP-haemocyanin challenge did not elicit memory responses. The IgG response component appeared to be inherited dominantly from the C3H/HeN parent. The IgM component resulted from genetic enhancement.

Notes: The effect of incompatibility for Mls determinants was studied in lethal graft-versus-host reaction (GVHR) in the mouse. GVHR was induced in adult recipients of the following H-2k strains: (AKR x B10.BR)F1 (MlsB/Mlsb); (C3H x B10.BR)F1 (Mlsc/Mlsb); (CBA/J x B10.BR)F1 (Mlsd/Mlsb) and (CBA/H x B10.BR)F1 (Mlsb). Recipient mice were heavily irradiated and grafted with bone marrow and spleen cells from H-2 compatible B10.BR (H-2k, Mlsb) or H-2 incompatible B10.D2 and B10 donors were normal, while those from B10.BR donors were either normal or pre-immunized against the recipient strains. In all experiments the survival of recipients with Mlsa/Mlsb and Mlsd/Mlsb phenotypes, and only in one experiment of those with Mlsc/Mlsb phenotype was greater and/or the survival time longer than that of recipients expressing only Mlsb. However, late deaths (〉 120 days post grafting) observed after grafting of normal B10.BR cells were more frequent in Mlsd/Mlsb than in Mlsb strains. On the other hand, when B10.BR donor cells were pre-immunized against H-2k compatible (AKR x B10.BR)F1 (Mlsa/Mlsb) or (CBA/J x B10.BR)F1 (Mlsd/Mlsb) strains, the survival time of H-2 incompatible (B10 x B10.BR)F1 (H-2b/k, Mlsb) recipients was longer than when donor cells were pre-immunized against (CBA/H x B10.BR)F1 (Mlsb) strain. We conclude that donor incompatibility for Mlsa or Mlsd or donor-pre-immunization against Mlsa or Mlsd exerts a protective effect on lethal GVHR developed across non-H-2 or H-2 barriers; the protective effect of Mlsc is less efficient or absent. The Mls-induced protective effect shows the following properties: (a) efficiency in vivo correlates with the capacity of the corresponding alleles to stimulate an in vitro MLR; (b) is efficient in either primary or secondary response to other minor antigens; (c) is not H-2 restricted; (d) is nonspecific; (e) disappears late after grafting; (f) with respect to the genetic background, the early protective effect is followed, late after grafting, by an opposite effect which increases the mortality, suggesting that M/s locus determinants are capable of activating several cell populations with different biological functions.

Notes: A long-term in vitro grown T cell line derived from a cotton-topped marmoset (Saguinus oedipus)) infected with Herpesvirus saimiri was found to share surface antigens with human amplifier T cells and to augment the capacity of human B cells to secrete immunoglobulin. This is the first demonstration of T/B collaboration across such a large phylogenetic barrier and might have interesting implications for understanding the nature of molecular interactions mediating cell/cell cooperation.

Notes: The segregation of genes controlling ECIA susceptibility and the level of immune response to native calf type II collagen were determined in the F2 progeny of matings between WF (RTIu/u; ECIA-susceptible; high responders) and LEW.B3 (RT1n/n; ECIA-resistant; low to intermediate responders). RT1n/n F2 progeny showed resistance to ECIA, low skin test reactivity to type II collagen and intermediate levels of IgG anti-collagen antibodies (-log2 of 6.2 ± 2.6; mean ± SD, n= 10). RT1u/u and RT1u/u F2 progeny were susceptible to ECIA and were high responders to type II collagen by skin testing and IgG antibody titres (-log2 of 12.1 ± 1.3, mean ± SD, n= 26). Although all rats that developed arthritis were also high responders to type II collagen one group of immature F2 progeny, RT1u/u and RT1u/n, showed high anti-collagen immune responses in the absence of detectable arthritis. The data indicate that genes linked to RT1.A control susceptibility to ECIA and at least part of the immune response to native calf type II collagen in WF and LEW.B3 rats.

Notes: Mice bearing the I-A subregion mutation bm12 were immunized and challenged with the α-subunit of human adult haemoglobin. Under conditions in which parental B6/Kh mice respond, B6.C-H-2bm12 mice are inhibited nearly 100% in their ability to respond to challenge to the α-chain of haemoglobin. D2.GD mice which express a variant Ae (Eβ) polypeptide of the I-E subregion can respond as well as B10.D2 mice to both subunits (α- and β-) of haemoglobin. These observations as well as other genetic mapping data confirm the I-A mapping of α-chain-specific Ir genes and extend the genetic fine mapping to the Aβ gene within the I-A subregion or a combinatorial Ia determinant generated by an interaction of Aα and Aβ. In addition they implicate the Ia.8 specificity in determining immune responsiveness to α-chain determinants.

Notes: Electrophoretic and serologic investigations of C4 in serum samples from a family material, showed that a weak, or partial, inhibition of anti-Rg sera, was an inherited property of some of the C4 haplotype products. The weak Rg activity was strongly, but not absolutely associated with the C4 FI and C4 I haplotypes.

Notes: Mouse oocytes at the dictyate stage were tested for the presence of H-2 antigens and Ia antigens, by means of indirect immunofluorescence. Oocytes reacted positively with NIH alloantisera, but were negative with anti-Ia region alloantisera. Results with monoclonal antibodies indicate very low antigen density on oocytes.

Notes: A Friend virus-induced tumour of BALB/c (H-2d) origin, HFL/d, was examined for the expression of alien H-2 antigens. The alloantigens on HFL/d were typed by generating CTL in primary MLC with HFL/d as stimulator and measuring reactivity to targets with known H-2 antigens, and confirmed by assessing recognition of HFL/d targets by CTL generated in primary MLC with stimulators expressing known H-2 antigens. Potential cross-reactivities between alloantigens were analysed by cold-target inhibition experiments. BALB/c cells stimulated with HFL/d lysed H-2b targets, and BALB/c anti-H-2b CTL lysed HFL/d; analysis with recombinant haplotypes demonstrated both H-2Kb and H-2Db alien antigens on HFL/d. C57BL/6 (H-2b) cells stimulated with HFL/d recognized H-2Kd, H-2Dd, and an additional determinant unique to HFL/d. (BALB/c x B6)F1 cells also recognised a unique HFL/d determinant not of H-2b or H-2d origin. These unique determinants, which induced a strong cytotoxic response in primary MLC, were not shared by BALB/c or B6 tumours induced by cross-reactive FMR viruses. Thus, HFL/d expressed the K and D antigens of its strain of origin, two typed alien H-2 antigens, and at least one other untyped antigen which may represent an additional H-2 determinant. These studies further demonstrate the utility of examining the reactivity of CTL generated in primary MLC to probe for the presence of alien H-2 antigens.

Notes: Properdin factor B is a genetically-controlled polymorphism that can be demonstrated by agarose gel electrophoresis. The Bf gene frequencies were determined for 194 blacks from the south-eastern United States. The frequencies for Bf-F, Bf-S, Bf-F1, and Bf-Sl are 0.626, 0.327, 0.034, and 0.013, respectively. The south-eastern blacks have similar Bf frequencies to the South African blacks; however, both these groups are different from blacks from Boston. The frequency differences between south-eastern blacks and Boston blacks may be due to racial admixture differences found in the two populations.

Notes: Fifty-seven members from ten families in which one parent and at least one child have asthma were studies with dilutional skin tests and RAST to grass pollens after determination of HLA haplotypes. We found no direct evidence for linkage of a hypothetical asthma locus with HLA or for a significant association of asthma with HLA haplotypes. Linkage between the HLA loci and a gene or genes which allow for the expression of clinical asthma could neither be proven nor disproven due to the small sample size. All of the asthmatic children had positive dilutional skin tests and RAST, suggesting that atopic asthma may be genetically controlled by the HLA chromosome (chromosome 6). Nonetheless, determination of the histocompatibility antigens can increase the value of predictive risk analysis for asthma. Such a determination may be important in the early identification of a child born to a family with atopic asthma.

Notes: T. OHTA; Evolution and Variation of Multigene Families.

Notes: The distribution of Glm(f, z, a and x), G3m(b0, b1, b3, b5, c3, c5, g, s and t), A2m (1 and 2) and Km(1) allotypic determinants in a series of Spanish blood donors. The following results were obtained: Gmz,a;gAm1= 0.199; Gmz,a;gAm2= 0.019; Gmz,a;bAm1= 0.081; Gmz,a,x;gAm2= 0.005; Gmf;bAm1= 0.677; Gmz,a;bAm1= 0.019 and Km1= 0.096. The results are similar to those reported for adjacent Basque and Portuguese populations. The origin of the Gmz,a;bAm1 haplotype is unknown.

Notes: Serolgoical and immunochemical assays detected antibodies to human la-like antigens in five out of five rabbit antisera to cultured human B lymphoid cells but did not detect them in five bleedings from two rabbits immunized with human peripheral blood lymphocytes. These results, which may reflect differential immunogenicity of la-like antigens from different cells, indicate that the presence of anti la-like antibodies in heterologous antihuman lymphocyte sera is not a general phenomenon as reported recently for animal model systems.

Notes: The murine Ly-4 locus is further described with the definition of both Ly-4.1 and 4.2 specificities and the demonstration of linkage of H-3 on Chromosome 2. As has been found for several other Ly-specificities, both Ly-4 specificities are absent from the thymus, but are found on peripheral T and B cells, with B cells having the greatest antigen expression. The expression of both Ly-4 specificities was influenced by an H-2-linked gene, mapping in or near the H-2D locus.

Notes: The factorial correspondence analysis, which is a descriptive statistical method, was used to study the preferential associations between locus HLA-A, B, C and Bf alleles. This method does not limit the number ofloci that can be studied and must therefore be considered as an interesting method of studying haplotypic associations within the HLA system.

Notes: Immunoglobulin was obtained from a hybridoma cell line, which was a reclone of a hybrid between a rabbit cell and mouse myeloma cell (X63-Ag8). The immunoglobulin, isolated from the cell culture medium was found to be homogeneous by isoelectrofocusing and immunoelectrophoresis and consisted of mouse heavy and rabbit light chains, linked by disulphide bonds. All immunoglobulin molecules carried both mouse and rabbit determinants; mouse determinants were associated only with the heavy chains while rabbit determinants were only associated with the light chains. The rabbit light chains were of Ab4 allotypical specificity, but possess only some of the Ab4 determinants normally present in Ab4/Ab4 animals. It was sugested that the restriction in allotypical specificity may be a general property of light chain Ab allotypes; the normal serum immunoglobulins may be heterogeneous with respect to the allotypic determinants and any one molecule may possess only a proportion of determinants detected by a conventional anti-allotype antiserum.

Notes: In a family study of coeliac disease, HLA types in fifty-three patients and their relatives were examined. There are no differences in HLA frequencies between child and adult patients. Comparison with a random series of normal controls shows increases frequencies in patients of HLA-A1 and B8, while the family material shows that there is also an excess of haplotype I-8. The excess of homozygotes is thought not to be a factor in the aetiology. Intrafamilial analysis shows that only B8 is significantly associated with the disorder. It is argued that the HLA association does not indicate a ‘coeliac gene’ but that the B8 allele is a major gene in a polygenic system affecting the disorder.

Notes: Several interesting and clinically important strains of Mus musculus were serotyped with alloantisera recognizing the different alleles of the Thy-1, Ly-1, Ly-2, Ly-3, Ly-4, Ly-5, Ly-6 and Ly-7 loci. The strains were the Biozzi high and low responder strains, of importance in immune responsiveness studies, and the strains BXSB, MRL and MRL—lpr/lpr—strains which spontaneously develop immune complex disease. In addition the related species Mus musculus castaneus was typed with the same reagents. The knowledge of the cell surface phenotype should prove useful in various functional studies involving these interesting strains.

Notes: Mouse strains differ widely in their natural killer(NK)-cell activity. In the (A X B6) X A backcross, high reactivity was linked to H-2b, although non-H-2-linked genes were also demonstrated (Petranyi et al., 1975). Harmon et al. (1977) demonstrated an H-2Dd-associated reactivity gene (1977). In the present study, we have tested eleven B10 congenic strains for NK activity. The H-2Dd strains B10.A, B10.T(6R), B10.S(7R), B10.HTT and B10.D2 were more highly reactive than B10, B10.S, B10.G, B10.A(2R) and B10.BR, which do not carry the d allele at the H-2D locus. While this confirms the H-2Dd association of a reactivity gene, an exception was found in the B10.A(5R) strain that was low reactive in spite of the fact that it carries H-2Dd. This suggests the possibility that the H-2Dd-associated gene is outside H-2, to the right of Tla.The AKR.H-2b congenic line had the same low activity as the AKR.H-2k strain; both were much lower than B6. This suggests either one of two possibilities: the H-2b-linked reactivity gene is relatively distant from the H-2 complex, although localized on chromosome 17 or alternatively, if localized within or in the close neighbourhood of H-2, it requires non-H-2 genes for full expression.Previously, we have shown that the B6 X DBA/2 F1 hybrid was more highly reactive than either one of its two parental strains (Klein et al., 1978). A similar complementation effect is described in the present paper for the B10.D2 congenic strain. The high reactivity of this line can be due to the combined effect of an H-2b-linked gene from DBA/2 and the non-H-2 background of B10 or, alternatively, the former, together with an H-2b-linked gene from B6 that lies well outside outside the H-2 locus itself.

Notes: The K region of the H-2 major histocompatibility complex (MHC) of mice of H-2Kk haplotype codes for two distinct alloantigens. One of these alloantigens, designated k-common, is expressed by C3HfB/HeN mice (C3Hf). The other alloantigen, designated k-unique, is not expressed by C3Hf mice. The H-2 haplotype of C3Hf mice has been classified as kv1 and the variant antigen distinguishing this strain from mice of H-2Kk haplotype has been designated kv1-unique. Several transplacentally-induced lung tumours of C3Hf mice express the k-unique, rather than the expected kv1-unique, antigen. The immunogenicity of the k-unique antigen on C3Hf-derived lung tumours varies with different tumours. In particular, the capacity of the k-unique antigen to induce radioresistant immunity in C3Hf mice appears to be lost on long term cultured tumour cells even though the tumour remains susceptible to in vivo immune responses directed against the k-unique antigen. Alterations in expression and in immunogenicity of unique H-2-coded antigens may dictate the nature and efficacy of immune surveillance of autochthanous tumours.

Notes: The inbred mouse strains BN/a and BN/b have haplotype H-2bp characterized by H-2.33 and lacking any other private specificity known in inbred strains. Two transplantable B cell leukaemias which originated in BN/a and BN/b mice treated with anti-lymphocyte globulin were tested serologicaly for H-2 antigens. Tests during passages 169-181 revealed several quantitatively different reactions with sera against public specificities, some of these being due to Ia antibodies. No change in expression of the private specificities was seen. On the other hand, during the later passages (239-258) a number of qualitative differences were seen, the most remarkbale being the loss of H-2.33 and gain of H-2.4, 31. The overall serological pattern of cells resembled that of H-2d rather than of H-2bp haplotyes and this was confirmed by absorption tests. The changes reported here may be due to alterations of repression and derepression pattern of the presumed multiple structural H-2 genes present in the genome.

Notes: Cellular cytotoxicity experiments were done to test the potential of the extra H-2 antigenic specificities on the K36 spontaneous leukaemia as targets. In addition, experiments were performed to rule out the possibility that the target determinants could be normal cross-reacting alloantigens, e.g., T1, Qa, non-H-2 and previously undetected H-2 public specificities, which are more readily detectable on tumours than on normal cells.We used F1 hybrid mice, in which one parent was of the strain of origin of the tumour (K36) and the other parent of the B10 congenic series, i.e., (AKR x B10)F1. These cells were stimulated by lymphoid cells from other B10 congenic strains, B10.A and B10.D2, and tested against the test tumour K36 and several PHA blast controls. Several K36 sublines as well as a cloned line of K36 (K36.16) were used and significant cytotoxicity against. an H-2d-like target on these tumour cells was obtained. These data exclude the possibility of a corss-reactive alloantigen, e.g., undetected H-2 public specificity, or differentiation antigens. These results with the K36 tunour were consistent with our immunochemical studies (see Schmidt & Festenstein, 1980) and were confirmed and extended by cold target inhibition experiments. In these experiments, B10.BR cells were sensitized by B10.D2 lymphoid cells and tested against B10.D2 (51chromium-labelled PHA balsts). Two kinds of normal unlabelled lymph node suspensions as well as the K36.16 tumour cell suspension were used. Significant specific inhibition of between 19% and 40% was obtained using K36 and between 23% and 37% using B10.D2 (positive conrol). AKR cells (negative control) in contrast were unable to reduce the precentage specific cytotoxicity.Since it was already known that the H-2Kk gene products are missing from this tumour (Schmidt & Festenstein, 1980), it was of interest to test whether cytotoxic effectors directed against the H-2kk gene products were able to kill the K36 tumour. Accordingly, B10.D2 lymphoid cells were sensitized to B10.BR (C3H.0H) and B10.A targets, respectively, and tested against K36 and appropriate controls. Only weak killing was observed when sensitization was effected against the K end of the H-2k haplotype (i.e., using B10.A as the sensitizing cell) but strong and significant cytolysis was found when the sensitization was against the whole H-2k haplotype or against the H-2Dk gene product. These results were confirmed by cold target inhibition studies.These experiments provide further indications for the H-2d-like characteristics of these allodeterminants. We have already excluded some of the possible explanations for these findings (i.e., corss-reactions with H-2 and non-H-2 normal specificities). The cold target inhibition experiments rule out non-specific viral effects. Thus, we favour an alteration in regulatory genes leading to repression of the H-2Kk product and derepression of the H-2Dd product, but cannot formally rule out highly corss-reactive H-2-like virally encoded determinants.

Notes: Alien H-2k-like antigens were found to be expressed by a methylcholanthrene induced tumour of BALB/c (H-2d) origin. H-2 specificities of the k haplotype were detected on this tumour by a variety of serological techiques, including 51Cr-release cytotoxicity, microradioassay and absorption. The antisera employed were conventional polyspecific alloantisera, typing sera with restricted specificty and monoclonal hybridoma-derived anti-H-2k antibodies.The tumour has a low expression of the private specificty 31, which characterizes Kd molecules, and does not seem to express the private specificities of Dd, Kk and Dk molecules. It appears to express predominantly alien H-2-like antigens which are very similar to but not identical with normal H-2k molecules.

Notes: The immune response of SJL/J (H-25) mice to syngeneic reticulum cell sarcoma (RCS) tumour cells was investigated. The nature of tumour-associated antigens was examined by immunological and biochemical techniques. Reticulum cell sarcomas of different origins (spontaneous, transplantable and cultured cell lines) stimulate a strong syngeneic response measured by [3H]-thymidine incorporation. However, only the cell line were able to stimulate a syngeneic cell-mediated cytotoxic response. Further analysis of the syngeneic response revealed that RCS cells express inappropiate alloantigenic specificities on their surface. Thus, evidence is provided which demonstrates that RCS tumour cells carry antigens which cross-react with BALB/c (H-2d) and C57BL/6 (H-2b) alloantigens. The presence of inappropriate antigens in the in vitro lines was detected by cell-mediated cytotoxicity, cytotoxic antibody and immunofluorescence whereas antigens on in vivo lines and spontaneous RCS were detected primarily by immunofluorescence. Conversely, H-25 expression on the in vitro lines was detected only by immunofluorescence whereas the H-25 of the in vivo lines were detected by cytotoxic antibody. By these assays inappropriate antigens were not detected on normal SJL/J lymphocytes. Immunochemical analysis of the inappropriate antigens by two-dimensional gel electrophoresis was performed with SJL/J anti-BALB/c and monospecific anti-H-2Dd sera. These sera precipitated 45,000 MW molecules from BALB/c lymph node cells and from SJL/J in vivo and in vitro RCS tumour which appeared very similar. The sera also precipitated molecules from SJL/J lymph node cells which resemble the BALB/c and RCS molecules. Thus, RCS tumours express inappropriate alloantigens which may be cryptic on normal cells. The biological significance of these tumour-associated antigens in vivo is discussed briefly.

Notes: Serological and structural changes of surface markers involved in immune reactions may occur in human and murine tumour systems. Thus nine out of twenty-one human tumour cell lines and SV40-transformed fibroblasts differed from autologous lymphoblastoid cells or fibroblasts in their reactivity with HLA allonatisera. H-2 antigens isolated from the murine tumour cells 6C3HED and TP 1422, undergo structural changes. An alien HLA-B7 was detected in sera from two melanoma patients. The serologic activity on H-2 antigens was significantly increased in the serum and ascites fluid of tumour bearing mice. Additionally, human SV40-transformed fibroblatsts acquire receptors for monkey red blood cells and the murine lymphosarcoma cells 6C3HED express receptors for sheep red blood cells.

Notes: Erythrocytes that exhibit the rare blood group p phenotype lack the P antigen (globotetraosylceramide) and the Pk antigen (globotriaosylceramide). This phenotype is inherited as an autosomal recessive condition and the red cells of heterozygous individuals, parents and children of p persons, are serologically normal but no chemical analyses of their red cells have been reported. We have studied an unusual family in which all five children exhibit the p phenotype. In addition to the abnormalities described previously, the erythrocytes of four siblings had twice the normal concentration of lactotriaoslyceramide and lactoneotetraosylceramide. These cells also contained 3-5 times as much sialosyllactoneotetraosylceramide and up to a two-fold increase in GM3 ganglioside. The glycolipids of the parents' erythrocytes were normal. Electrophoretic analysis of the glycoproteins of the proposita's erythrocytes revealed no abnormalities, but her erythrocyte membranes contained approximately 35% less galactosamine than normal red cells. This abnormality resulted from a marked decrease in galactosamine that was soluble in chloroformmethanol. The lipid-extracted residue, which contained the glycoproteins, had a normal galactosamine content.

Notes: The identity and complete purification of mouse Thymocyte Interaction Modulation Factor (T IMF) is described. Use of silver-stained PAGE methods shows that previous methods of purification yield preparations containing two protein or glycoprotein bands. T IMF activity from H-2k mice can be bound to 15.5.5 monoclonal antibody columns (anti H-2 Dk) but not to 11.4.1 columns (anti H-2 Kk). The activity can be recovered from 15.5.5 columns and runs on PAGE as a single band at approximately 34,000 Daltons. This evidence together with previous evidence relating the activity to H-2 D locus argues that T IMF is a soluble H-2 D antigen fragment equivalent to a papainized H-2 fragment. Additional evidence is presented on an improved method of assay of T IMF activity, on its inactivation by enzymes and serine-esterase inhibitors and of its effect on syngeneic leucocytes and macrophages. It is also shown that T IMF is not appreciably toxic for cells.

Notes: One hundred and sixty-five individuals with ragweed rhinitis and asthma were studied. The associations between the HLA system and: Ra3 skin-test response, Ra3 RAST, Ra3/antigen E skin-test reactivity ratio, Ra5 skin-test response, Ra5 RAST, Ra5/antigen E skin-test reactivity ratio, serum IgE levels, antigen E skin-test response, and antigen E RAST were studied. In addition, the influence of the serum IgE levels of these immune parameters were evaluated. No highly significant associations were noted.

Notes: We have previously shown that the antibody response to mammalian myoglobins is under genetic control. In the present study we examined antibodies to sperm-whale, Atlantic bottlenosed dolphin, Black Sea dolphin, horse and badger myoglobins, raised in high responder strains of mice, to ascertain whether there is genetic control of antibody affinity to mammalian myoglobins. Using antisera of varying dilutions, the binding to 125I-labelled homologous myoglobins was studied by inhibition with homologous myoglobin over a wide range of inhibitor concentration in a modified Farr assay. The results indicated that there are no large differences between high responder strains of mice in the affinity of antibodies to mammalian myoglobins.

Notes: No. Gm, Am, Pi, and Km gene frequency difference has been observed between eighty-seven Caucasin IgA nephropathies and ninety-six controls. But a Km1 significant increase is found in patients with chronic renal failure compared with the total patients group. This data fits for a genetic predisposition factor in IgA nephropathy.

Notes: The genetic control of the in vivo growth of the Moloney virus-induced BALB/c lymphoma YC8 was studied in F1 hybrids between BALB/c and several strains differing at the MHC and/or at the level of non-H-2 genes. Parental strains of the B10 and C3Hf but not of A, BALB/c or DBA/2 backgrounds introduced a significant resistance to the growth of 102 YC8 cells (a dose able to kill 100% of BALB/c mice) in semisyngeneic hosts. This resistance appeared to be due to non-H-2 genes although a modulation of the tumour growth by genes encoded by the MHC was also evident. The study of backcrosses between susceptible BALB/c and resistant (BALB/c x B10.BR)F1 crosses revealed that 83% of animals developed lethal tumors after injection of 102 YC8 cells. This high frequency of tumour takes was not linked to genes of the MHC. Adult thymectomy plus sublethal irradiation was able to abrogate the resistance of (BALB/c x B10.BR) or (BALB/c x B10.RIII)F1 mice to YC8 growth. Since the injection of silica also impaired the resistance to YC8, we tentatively concluded that the genetic control of resistance to YC8 is mediated both by T cells and macrophage-like cells.

Notes: Mice of independent haplotypes and several recombinant inbred strains were immunized with highly purified preparations of either the α-chain or β-chain subunit of human adult haemoglobin. Cells from the sensitized lymph nodes were challenged in vitro with the appropriate subunit (or in some cases both chains) and cell proliferation assessed by 3H-thymidine incorporation. Mice of the H-2b and H-2d haplotypes were high responders to α-chain while mice of the H-2f, H-2j, H-2k, H-2r, H-2s, H-2u, and H-2v haplotypes were low responders. The low responsiveness of B10.A(4R) and B10.MBR and the high responsiveness of B10 indicated that the Ir gene(s) determining responsiveness to the α-chain subunit resides in the I-A subregion of the mouse major histocompatibility complex. Mice of the H-2d, H-2f, and H-2s haplotypes were high respoders and H-2b, H-2f, H-2q, and H-2u haplotype mice were low responders to β-chain. H-2k, H-2p, H-2r, and H-2v haplotype mice were intermediated responders to β-chain. The low responsiveness of B10.S(8R) and B10.TL and the high responsivenes of B10.S(9R) mapped the Ir gene(s) to β-chain to the I-A subregion. Data collected from challenging high responder cells with both subunits indicated that α-chain and β-chain do not crossreact. These results are discussed in reference to earlier observations suggesting that the low responsiveness of some strains of mice to priming and challenging using the intact haemoglobin molecule might be due to a negative regulatory influence mediated by one of the subunits. In the absence of this influence these mice would respond normally.

Notes: An attempt to determine association between immunoglobulin allotypes and Schistosoma japonica infection was made. The results show that no apparent relationship exists.

Notes: Diet and Resistance to Disease; Advances in Experimental Medicine and Biology. Vol. 135. M. Phillips and A. Baetz

Notes: The antigenic specificities of six (1-6) IgG allotypes of the domestic mink were tested in the sera of closely related species of Mustelidae family and distant mammalian species. It was found that allotypes 1 and 5 are ancient. Their antigenic specificities were established not only in Mustelidae, but also in other taxonomic orders of mammals. Allotypes 3 and 2 are phylogenetically younger; they were detected only in Mustelidae. Allotypes 4 and 6 appear to be unique to the domestic mink.The instantaneous evolutionary emergence of complex allotypes 4 and 6 is difficult to explain by a rapid accumulation of gene point mutations during phylogenesis. Activation in the domestic mink of those immunoglobulin genes, which are silent or poorly expressed in closely related Mustelidae, is suggested as a more plausible explanation.

Notes: In the V/V type of bovine erythrocytes (BE), the antigen IM and the Thomsen-Friedenreich (TF) receptors, which reacted with a TF-specific agglutinin from human sera and the lectin from Helix pomatia, were all destroyed by treatment with trypsin. Unlike the V/V, in the F/F type of BE the antigen IM and these TF receptors were not only not destroyed by trypsin, but this enzyme treatment was, in fact, necessary to make them amenable to the corresponding agglutinins.Another TF receptor, which reacted with the lectin from peanuts, was identified on a trypsin-resistant component of all BE and independently of the FV genotypes.

Notes: Five major glycoproteins with anti-B agglutinin activity were isolated from seeds of Euonymus Sieboldiana by a procedure based on precipitation with ammonium sulphate, Sepharose 4B gel filtration, CM- and DEAE-Sepharose chromatography and Sephacryl S-200 gel filtration. The purified glycoproteins each gave a single symmetrical peak on Sephacryl S-200 gel filtration with elution volumes corresponding to molecular weights of approximately 15,000 to 130,000, each forming a single precipitin line on gel diffusion plates with anti-E. Sieboldiana antibody. These anti-B glycoproteins were rich in acidic amino acids without cysteine and methionine and contained about 8-36% carbohydrate, of which galactose, arabinose and glucose were the predominant sugars, with small amounts of glucosamine, rhamnose, fucose, xylose, mannose and ribose. The most anti-B active lectin agglutinated human B red blood cells at a concentration of 2 μg/ml and was strongly inhibited by melibiose. The three other lectins with anti-B agglutinin activity, however, were not inhibited by any galactose-containing glycosides.

Notes: Linkage between the Pi (alpha1-antitrypsin) and Gm (immunoglobulin heavy chain) loci was studied in thirty-four families including forty-one informative parents and 142 children. In females, the results did not provide evidence for linkage (posterior probability of non-linkage 0.98). In contrast, in males, there was strong evidence for linkage (peak lod 3.9 at 0= 0.18, posterior probability of linkage 0.98). The two populations appeared to be significantly different (0.001 〈 P 〈 0.01) with respect to the heterogeneity criterion of Morton. In addition, the effect of the possession of the S allele (associated with significantly decreased serum alpha1-antitrypsin levels) was studied in fifteen informative parents and fifty-three children of the same group. No evidence for or against linkage was found in females, but in males close linkage between Pi S and Gm was demonstrated (peak lod 7.7 at 0= 0.05, posterior probability of linkage 0.9999). These data indicate significant linkage between Pi and Gm in males but not females and close linkage between the Pi S and Gm markers in males.

Notes: Cytotoxic antibodies to HLA-A,B,C and to Ia-like antigens were detected in about 8% of sera drawn from 1312 women several years after their last pregnancy. In the majority of sera anti Ia-like antigen antibodies were not associated with anti HLA-A,B,C antibodies. Persistence of both types of antibodies was not correlated with the number of pregnancies and with the time interval between the last immunizing stimulus and the drawing of the sample. Testing of the sera with a panel of HLA typed lymphocytes identified 20 sera specific for HLA-A,B alloantigens and 7 specific for Ia-like alloantigens.

Notes: The evidence of the past 10 years indicates that genes mapping in the I region of the mouse major histocompatibility complex (H-2) regulate a bewildering array of immunologic functions. A survey of H-2-linked specific immune response (Ir) genes shows that the phenotypic effect of these genes is to enable a particular inbred strain to discriminate and recognize remarkably precise chemical specificities, such as one or two amino acid interchanges in a polypeptide chain. The only I region gene products which have been identified to date are the Ia antigens. These include five readily detectable polypeptide chains (Aa, Ab, Ae, Eα, and Ii) and several other serologically distinct entities which are selectively expressed on functionally distinct T cell subsets (J1, J2?, J3? and C). The specificity of recognition of Ir genes would seem to require a larger number of I region gene products than can be generated even by combinatorial association of the four readily identifiable peptides (to give eight combinatorial associations) and the other serologically identified gene products. If the Ia antigens are to function as an antigen specific receptor system, separate from immunoglobulin molecules, there must be other, as yet undetected, I region gene products (e.g. Ia antigens). Alternatively, the known I region gene products could function by any one of several postulated mechanisms to generate an antigen specific T cell receptor system. The available evidence for the total number of I region gene products is reviewed, and the alternate possibilities are briefly discussed in this presentation.

Notes: Different patterns of tumour growth resulted from inoculation of separate isolates of the Subgroup C Bratislava 77 strain (B77) of Avian Sarcoma Virus (ASV) into three closely-related inbred lines of chickens. The major genetic difference between these chicken lines is that each is homozygous for a different MHC haplotype. Since for one of the viral isolates, resistance to progressive tumour growth has been shown to be controlled by MHC-linked genes, the data presented here suggest that MHC-controlled tumour rejection operates on viral or cellular determinants different from those which define classical viral group or subgroup specificity.

Notes: The red cells of a normal male blood donor, K.S., were first grouped as B but he was found to lack anti-A in his serum. Closer investigation revealed that his red cells had very weak A activity, demonstrable only by absorption and elution of anti-A. He is a non-secretor of ABH and a secretor of Lea. Blood group A-, B and H-gene specified glycosyltransferases were detected in his serum. In contrast to the finding of a B antigen of normal strength on his red cells, the B transferase in his serum was only about 30% of the normal level and, despite the very weak A activity of K.S.'s red cells, the A transferase level was about 50% of that found in the serum of group A individuals with normal strength of A antigen. Moreover, the A transferase on the basis of its pH optimum, Km values for donor and acceptor substrates, activation by divalent cations, isoelectric focusing profile and capacity to convert O to A-active cells, was characterized as the product of an A1 gene. A family study showed that K.S.'s wife is group A2 and that they have two sons, one group A2 and the other group B. The group B son is assumed to have inherited a B gene from the propositus but the level of B transferase in the son's serum is three times as high as that in his father's serum. The wife of the propositus and his group A2 son have normal A2 transferases in keeping with their A2 red cell status. The A2 son therefore appears to have inherited an A2 gene from his mother but neither the A1 nor the B gene shown to be carried by his father. The distribution of transferase activities in K.S.'s red cells differs from that in his serum. A level of B transferase within the normal range was found in his red cell membranes but a very low level of A transferase was detected. The discrepancies between the serum transferases and ABO-red cell group, together with the pattern of inheritance within the family, led to a suspicion of chimaerism. This was confirmed by the finding of fibroblasts with the female 46XX karyotype in cultures of the propositus' skin. These results suggest that K.S. is a dispermic chimaera with two different cell lines of the genotypes BO and A1O or A1A1. The group A2 son is assumed to have inherited an O gene from his father. It seems probable that K.S.'s bone marrow and reproductive organs are comprised predominantly of the XY cell line which carries the blood group BO genotype whereas his skin and other tissues which contribute the A1 transferase to his plasma, are partly made up of the XX cell line which carries the blood group A1O or A1A1 genotype.

Notes: A cloned hybridoma, producing an IgM kappa antibody, has been derived from a fusion between NSI myeloma cells and spleen cells from BALB/c mice immune to CBA lymphocytes. Its specificity for Lyt-1.1 alloantigen has been established from (1) the lymphoid tissue distribution restricted to T cells and (2) the reactivity pattern on a panel of thymocytes from standard and Lyt congenic mouse strains.

Notes: Haemagglutination inhibition studies using isolated membrane components from rat red blood cells showed that the activity of the major antigenic system RT2 was contained exclusively in the glycoprotein fraction and confirmed immunochemically the existence of two alleles, RT2a and RT2b. The SDS-PAGE analysis of the membrane showed two interconvertible glycoproteins of apparent molecular weight 72,000 and 36,000, and the higher molecular weight component appeared to be a dimer of the lower molecular weight one. Analysis of the various membrane preparations after 125I-labelling showed that the glycoproteins existed in at least two molecular species on the surface of the red cells and that one species was more readily radio-iodinated and dimerized than the other. The RT2 antigenic specificities were preferentially associated with this component.

Notes: Spleen cells from C3HfB/HeN mice (H-2kv1) were markedly less susceptible to lysis by monoclonal anti-Kk antibody (Clone 11-4) than spleen cells from C3H/HeN mice (H-2k). Less than 50% of C3HfB/HeN cells were lysed even at the highest antibody concentration tested compared to 70% of C3H/HeN cells. The difference in end point titre of the antibody tested on cells from the two strains was 5-10-fold. Similar differences were not observed using the conventional H-2Kk-typing antiserum (D-23).

Notes: F. H. BACH, B. BONAVIDA, ELLEN VITETTA, AND C. F. Fox; T and B lymphocytes: recognition and function. Academic Press, New York, 1979. ISBN 0-12-069850-1, Price U.S. $36.50.

Notes: Morphological studies of metaphase chromosomes were done with rats derived from the BIL/1 strain, which has genes affecting growth and reproduction linked to the major histocompatibility complex by conventional Giemsa-trypsin staining and the results were compared to rat strains not carrying these defects. A subterminal-terminal centromeric polymorphism was detected in chromosome 3 [del 3 (pter → cent)] among the strains studied. Comparison of the G-banded karotypes of the rats carrying the defects with the karotypes of the otsher strains did not reveal any gross chromosomal abnormalities.

Notes: C4-coated Ch(a+) red blood cells (RBC) were used as indicator cells in a serum inhibition reaction of anti-Cha, for the determination of the Ch group of serum. This serological study, combined with electrophoretic studies of C4 in a family material, showed that the C4M haplotype product was associated with partial inhibition of anti-Cha.

Notes: Individuals with selective absence of IgG1 and IgG2 were discovered by testing for allotypes and isotypes of the respective sub-classes. These individuals were homozygous for sub-class deleted Gm-Am haplotypes, as shown by allotype studies in two families (Gm-;…;g;A2ml/Gm-;n;b;A2ml and Gm-;n;b;A2ml/Gm-;…;b;A2ml) and by a population study of New Guineans (Gm fa;-;b;A2m2). The individuals with IgGl sub-class deficiency showed elevation of IgG2, IgG4 and in particular of IgG3.Gene deletion can result from unequal crossing over which renders a complementary chromosome with a duplication of a sub-class gene. In one family, duplication of γ3 genes was observed to have happened in one of a twin pair. Quantitation of sub-classes in families with γ1- and with γ3-duplicated haplotypes did not show increased levels of the gene involved.

Notes: A hybrid cell line R3/41-10 was produced by fusing a mouse myeloma line with spleen cells from CBA/H mice which had previously been immunized with human peripheral blood lymphocytes (PBL) obtained from a single donor. Hybrid secreting antibodies to lymphocyte antigens were detected by assaying the culture supernatant for antibody binding to the donor PBL. Those lymphocytes binding more than ten times the background were cloned in soft agar and transferred to micro-culture plates (Limbro). Antibodies from some wells lost their binding activity. Antibodies from other clones, although retaining their binding capacity, were multispecific in cytotoxicity experiments, killing all the lympoid cells from a panel of normal donors; yet a third kind gave specific limited reactions. Supernatants from clones R3/41-10 and R3/41-13 gave concordant cytotoxic reactions killing 20-40% of the PBL. There was no cytotoxicity of Ig+ cells (B cells). Lymphocytes from seven out of fourteen normal donors reacted with the antibody. The specificity of the antibody produced by clone R3/41-10 was confirmed by absorption studies.The monoclonal antibodies (Mc+b) described in this communication are shown to react with a subpopulation of T lymphocytes of some individuals and not others, suggesting that they are detecting a polymorphic system of alloantigens like the Ly system in the mouse, provisionally designated HT-Ly. l.

Notes: Subcutaneous (s.c.) immunization of mice with viable allogeneic H-2 compatible spleen cells can induce a persistent state of delayed type hypersensitivity (DTH) to minor histocompatibility (H) antigens which can be evaluated with a footpad swelling assay. The importance of H-2 compatibility of the injected spleen cells with the recipient for (1) the elicitation of the DTH-reaction, (2) the induction of DTH-related effector and memory T cells and (3) the activation of T memory cells was examined with congenic mouse strains. Spleen cells sharing either the K or D region of the H-2 complex with the recipient could elicit strong DTH-reactions to minor H antigens, though somewhat less than did fully H-2 compatible allogeneic spleen cells. H-2 incompatible cells or cells only sharing I-region coded antigens elicited relatively weak, though significant, DTH-reactivity to the minor H antigens. Similar H-2 requirements for recipient mice were demonstrated in the immune lymphocyte transfer assay. Optimal induction of primary DTH and DTH-related T memory cells for minor H antigens also required H-2 identity of the immunizing cells and the recipient. To some extent, H-2 incompatible cells were able to induce primary DTH-reactivity and memory for minor H-antigens. The secondary DTH-reactivity was not or slightly dependent on the H-2 haplotype of the cells used for booster injection.It is concluded that the DTH-related effector cells are restricted in their recongnition of minor H antigens by K- or D-region-coded antigens. Presumably, macrophage processing of the allogeneic spleen cells after primary and secondary immunization accounts for the capacity of the minor H antigens to activate unprimed T cells and memory T cells when these antigens are presented on H-2 incompatible cells.

Notes: Difference in the amounts of H-2K.5 antigens present on erythrocytes was observed, using quantitative absorption method, among several B10 congenic strains. However, no such variation was seen on the lymphocytes and lung cells. The variability in the amount of this antigen on the erythrocyte surface was primarily dependent on the haplotype of the H-2K end in the B10 recombinant strains examined. This suggests that the regulator of H-2 expression on erythrocytes is in this region. Further genetic analysis confirmed that this regulation functions in the cis-position. Finally, the H-2K.5 antigenic activity was expressed on the reticulocytes of all strains tested, but appeared lower in the type 2 group indicating that the regulation begins early in erythropoietic differentiation and eventually results in a complete loss of detectable activity.

Notes: A two-step procedure employing gel filtration and anion exchange chromatography has been utilized to isolate LMW immunoglobulin from the horned shark, Heterodontus francisci. Light chains obtained by complete reduction and alkylation of the parent protein have been compared by several analytical techniques. Amino acid composition data implies a limited degree of variation in the light chains isolated from individual animals. Polyacrylamide gel electrophoresis of the CNBr digests of the light chains reveal indistinguishable banding profiles of the major peptides. Isoelectric focusing indicates limited heterogeneity in the light chain spectrotype and identity in the pI of the majority of bands detectable by staining. The suggested degree of structural similarity in the light chains of this phylogenetically primitive shark is discussed in terms of the evolutionary position of the species and current theories concerning the origins of structural diversity in immunoglobulins.

Notes: The mechanism of neonatally induced transplantation tolerance was studied in two mouse strain combinations involving differences at the D region of the H-2 complex only or at the same D region plus I-J subregion (including I-E, I-C, S and G regions). In the strain combination with the H-2D difference only, cells from tolerant mice proliferated markedly in the MLR assay when incubated with antigens tolerated in vivo, whereas the MLR reactions were negative in the combination with D plus I-J region disparities. In the latter combination cells from tolerant mice also did not respond to third-party antigens and their incubation with the tolerated antigens led to the suppression of cell proliferation. This non-specific suppression was absent in cells from tolerant mice in the strain combination, which differed in I-C, S, G and D alloantigens. Specific suppressor cells, which inhibited the development of cytotoxic cells, were demonstrated in tolerant mice of both strain combinations. The results show that, in addition to the specific suppressor cells induced by H-2K or H-2D alloantigens, non-specific suppressor cells induced by the I-J region disparity that may regulate the resultant activity against H-2D (and probably also H-2K) alloantigens are involved in transplantation tolerance.

Notes: We have used a combined serologic and structural approach to study the distribution of I-region associated (Ia) antigens in nine strains of inbred and partially inbred guinea-pigs. All of the inbred strains studied with the exception of strain 2 animals were found to share one or more I-subregions with inbred strain 13 animals. The BIOAD, R9, OM3, and BIOAC strains have the same I-region as strain 13 animals; the B/Lac strain has two subregions in common with strain 13, while the BIOB strain has a single subregion in common with strain 13. The availability of a number of different guinea-pig strains with well characterized major histocompatibility complexes should facilitate the continuing use of this species in studies of immunogenetics, transplantation, and tumour immunology.

Notes: Two-way and one-way mixed lymphocyte cultures (MLC) with Chinese Hamster peripheral blood lymphocytes were performed. Reduction of the culture surface and addition of 2-mercaptoethanol to the culture medium gives a marked enhancement of the reactivity of low numbers of lymphocytes in the MLC. Genetic analysis of the mixed lymphocyte reactivity (MLR) in the animals studied so far indicates that three or four different alleles are involved. Howerver, not all phenotypes could be traced. The samples of different stocks of Chinese Hamsters in Europe and the United States did not all share the same alleles and the samples were also different as regards the relative frequency of phenotypes. For DNA inhibition in stimulating cells mitomycin C treatment is less suitable than irradiation. Skin graft survival time was longer in animals which showed no MLR than in animals with a positive MLR.

Notes: The genetic basis of the restriction imposed on T cell mediating acquired antimicrobial resistance and delayed-type hypersensitivity (DTH) to Listeria in the rat was investigated. Sharing of MHC-coded genes between donors of sensitized T cells and antigen-stimulated recipients was both necessary and sufficient for efficient transfer of both resistance and DTH. Evidence to support this assumption was derived from experiments involving allogeneic transfers within major histocompatibility complex (MHC)-compatible strains and across MHC-barriers. Further support came from linkage studies with backcrossed rats and with the progeny of F1 rats mated with an unrelated strain. An unexpected difference in the compatibility requirements for effective transfer of DTH and resistance was noted in experiments involving the BI strain (formerly called B3). Thus, while B-region compatibility was obligatory for expression of DTH in recipients of sensitized T cells, considerable levels of protection could be transferred to either A-region or B-region compatible hosts.

Notes: The antibody response in mice to type I calf skin collagen is quantitatively determined by genes which map to the I region of the H-2 histocompatibility complex. The use of H-2 recombinant B10 congenic strains of mice reveals that a gene in the IA subregion and a gene to the right of the IA subregion affect responsivenss. To examine complementation patterns in the antibody response to collagen, five B10 congenic strains, each bearing an independent H-2 haplotype, were intercrossed to obtain nine hybrid strains heterozygous at the H-2 locus. In five combinations heterozygous progeny produced significantly greater antibody responses than those observed for the homozygous parental strains. Two low responder haplotypes, H-2k and H-2d, were shown to be qualitatively different. Mice of these haplotypes show a different dose-response pattern and a different phenotypic pattern of inheritance with respect to the high responder H-2b haplotype. Complementation effects found in F1 hybrid mice derived from H-2 recombinant parental strains indicate that high responsiveness, controlled by an IAb subregion gene, can be influenced by an interaction between an IAk subregion gene and an ICd subregion gene on different chromosomes. These data are consistent with the possibility that there exist two or more I region genes that have distinct functions and can interact to affect the levels of immune responsiveness.

Notes: A study of Gm allotypes in a Caucasoid family with hypogammaglobulinaemic probands, showed qualitative (unexpected or lacking Gm allotypes) and quantitative (increased or decreased Gm contents) abnormalities in many relatives. Part of these observations can be most probably accounted for by inheritance of a Gm1,17;5,28 haplotype, not described in Caucasians yet, and by an in vivo expression of latent Gm genes.

Notes: α-L-Fucosyltransferases were demonstrated in human saliva which catalyze the transfer of L-fucose from GDP-L-[14C]-fucose to oligosaccharides from human milk. An α-(1→4)-L-fucosyltransferase that synthesizes lacto-N-fucopentaose II and lacto-N-difucohexaose I from lacto-N-tetraose and lacto-N-fucopentaose I, respectively, was detected in saliva samples of Le(a-b+) secretors and Le(a + b-) non-secretors in which Lea substance was secreted. This enzyme activity was demonstrable neither in saliva samples of Le(a-b-) secretors nor non-secretors. An α-(1→2)-L-fucosyltransferase, that synthesizes lacto-N-fucopentaose I from lacto-N-tetraose, was detected in saliva samples from Le(a-b+) secretors which secreted H and Leb substances and from Le(a-b-) secretors which secreted only H substance. An α-(1→3)-L-fucosyltransferase was present in all saliva samples of different ABO and Lewis blood groups, irrespective of their ABH secretor status of the donors. The fucosyltransferases in saliva were activated by Mn++ or Mg++ ions, and were inhibited by ATP, GTP and EDTA. They had a broad pH optimun between pH 5.0 and 6.5.

Notes: Genes in the D region of the murine major histocompatibility complex, H-2, confer resistance to radiation-induced leukaemia virus. H-2D gene control appears to ensue at a step subsequent to virus infection, since elimination of virus infected cells does not become apparent until 3-5 weeks after virus infection. Nonetheless, almost immediately after virus infection, expression of H-2D-coded antigens is markedly elevated on the surface of thymocytes from resistant (H-2Dd) but not susceptible mice (H-2Ds or H-2Dq). This increased H-2D antigen expression triggers a vigorous cell-mediated immune response which probably plays a key role in resistance to leukaemia via elimination of virus-infected cells. A hypothesis is put forth to explain the induction of increased sythesis and expression of H-2D antigens. This hypothesis postulates that the oncogenic segment of RadLV bears a close resemblance to H-2.4, the private specificity for H-2Dd, allowing it to integrate at or near the H-2Dd murine gene. Subsequent to integration, the rates of transcription and translation are altered with a resulting increase in cell surface antigen expression. Other possibilities are also discussed.

Notes: When testing the serum of an individual anti-H-2 immunized mouse (B10 x A.SW)F1 anti-B10.M by the routine micro-lymphocytotoxicity test on lymph-node cells, unexpected antibodies were found. The most striking finding was that after absorption of anti-H-2.8 antibodies with B10.A(2R) (Kk) cells, antibodies remained which reacted with AKR, B10.AKM and B10.A V + mice while B10.A V-, B10.BR and C3H mice were negative. While all these strains share the Kk allele, only the positively reacting strains express high titres of infectious RNA turnover viruses. Unexpected reactions were observed also with H-2d, H-2j and H-2r cells and absorption experiments indicated two or three antibody populations.These reactions could be interpreted by two different possibilities: (1) anti-H-2 antibodies react with virus-altered H-2 structures; and (2) antiviral antibodies react with H-2 structures complexed with viruses. These possibilities should be taken into account when H-2 sera are tested on tumour or virus-infected cells.

Notes: Cytostatis of the H-2d tumour LSTRA by H-2-restricted effector lymphocytes was inhibited by antisera against H-2.4 and H-2.31 but not by antisera against public specificities or non-H-2 antigens. The unexpected reaction of the same effector cells against Gardner tumour (H-2k) was also shown to be inhibited by a combination of antisera against H-2.4 and H-2.31 but not by each antiserum used separately. The inhibitory capacity of these antisera was removed by absorption with B10.D2 but not with B10 lymphocytes. This indicated the presence of H-2d-like specificities on gardner tumour which could function as self-recognition structures in an H-2Kd and H-2Dd restricted system.

Notes: The specificity of he corss-killing exerted by cytotoxic T lymphocytes (CTL's) generated against H-2 region products was investigated in a 51Cr release assay on a panel of target cells from a number of different H-2 haplotypes.Their pattern of reaction shows that: (1) The target cells, expressing public specificities (H-2.28, H-2.1, H-2.5, H-2.3 or H-2.8) which should, theoretically, be recognized by the CTL's were killed, while those expressing no public specificities, recognized according to the H-2 chart by the CTL's wer not killed. (2) The CTL's generated against the H-2.28 specificity expressed on the D region products cross react with target cells expressing this specificity in their K region products and vice versa. The same phenomenon was observed with the H-2.1 specificity. These results provide evidence that public specificities are targets for CTL's. Antiserum reacting against the public specificity recognized by the CTL's was found to block the cross-killing, however, to the same extent as antisera directed against any specificity recognized by the CTL's was found to block the cross-killing, however, to the same extent as antisera directed against any specificity (private or public) expressed on the same molecule as the target determinant. Finally both the inhibition studies using anti-H-2 antisera and the direct cytotoxic assays showed that the public specificities of the H-2.28 family carried by the H-2.D and H-2.L molecules were recognized by different subpopulations of CTL's.

Notes: The problems of prevention and therapy of cancer are far from being solved. Regarding therapy, it is beyond doubt that surgery and radiotherapy cure a certain percentage of cancer patients. Cancer chemotherapy with the conventional cytostatic agents is a further means by which oncologists can help patients. Immunotherapy, including the newest methods of treatment with thymosin, and particularly interferon, may bring further progress. In the field of prevention of cancer mortality, early detection of precancerous and cancerous lesions and elimination of carcinogenic agents are up to now the most successful means. The continuing high mortality of cancer, even in the most developed countries, underlines the still unsatisfactory medical methods at our disposal. New approaches to the cancer problem are badly needed. It is the purpose of this conference to acquaint us with the basic research work done in the field of retinoids. The retinoids (vitamin A and analogs) represent a fairly new development in the cancer field, offering a new approach differing markedly in their more physiological mode of action from the hitherto existing approaches in prevention and therapy of cancer.

Notes: Abstract. The histopathological changes in the eye due to the penetration and growth of the parasite, Lernaea piscinae, in the host tissue of big head carp is described. Distinct pathological changes were hyperplasia of the corneal epithelium, severe inflammatory response mainly around the anchor of the parasite, in the anterior chamber, the corneal stroma and the vitreous body and detachment of the vitreous and retinal layers. Rupture of the lens capsule and fibrous tissue response around the process of the anchor structure of the parasite were also observed. The development of an immune response to the parasite within the body of the host is thought to have led to the infection of the cornea, an avascular site.

Notes: Abstract. Steelhead trout were exposed to sublethal concentrations of copper and inoculated with Yersinia ruckeri. Copper exposure at 7 and 10 μg/1 for 96 h caused more fish to die of infection than control fish (no copper). Infection susceptibility increased with time of exposure to a single dosage of copper (10 μg/1), reaching a maximum at 48 h. Lowering the copper concentration to 5 μg/1 caused the infection susceptibility to occur at 24 h. The infectious dose of Y. ruckeri was lower in fish exposed to 10 μg/1 copper for 48 h than control fish.

Notes: Abstract. Four species of flatfish [plaice, Pleuronectes platessa L.; turbot, Scophthalmus maximus (L.); Dover sole, Solea solea (L.) and the common dab, Limanda limanda (L.)] were experimentally infected with cercariae of Stephanochasmus baccatus under similar conditions and examined at intervals up to 7 weeks post-infection- The tissue response was found to be qualitatively the same in all four hosts and was consistent with a chronic granulomatous inflammatory reaction induced by resistant particulate foreign bodies. The intensity and rate of the response varied between host species but the capsule formation was essentially similar in all. The mature capsule consisted of an inner layer composed of leucocytes which underwent epithelioid transformation. The cellular structure of this tissue gradually degenerated from the oldest layer to form a dense eosinophilic ground substance in which was embedded nuclear debris. The outer layer of the capsule consisted of fibroblasts and reticulin collagen fibres. Muscle and fin cysts differed, with muscle cysts tending to be less discrete and more fibrous. The rate and intensity of the response to the parasite varied between different host species. Plaice and turbot showed the most intensive response and in turbot the reaction was considerably accelerated. Mortality of encysted metacercariae was only seen in turbot. The overall effect on larger 1-group fish was minimal, but the smaller 0-group plaice were more severely affected by the relatively large cvsts that interfered with organ function.

Notes: Books reviewed in this article:Fischkrankheiten 4th edn. By W. Schäperclaus. Akademie Verlag, Berlin, 1979, 2 volumes, 1089 pp.Ecology of Freshwater Fish Production. Ed. by Shelby D.Gerking. Black well Scientific Publications, 1978, 520 pp.Diseases of Fishes. Book 6. Fungal Diseases of Fishes. By G. A. Neish & G. C. Hughes. TFH Publications, New Jersey, 1979, 159 pp.Developments in Deep-Sea Biology. By N. B. Marshall. Blandford Press, Poole, Dorset, U.K., 1978. 566 pp.

Notes: Abstract. The transmission of Yersinia ruckeri has been investigated in steelhead trout using asymptomatic carriers of the causative bacterium of enteric redmouth disease. It was found that unstressed carrier fish did not transmit the bacterium to recipient fish to cause either an epizootic or produce new carrier fish. However, when the carriers were stressed with heat, the bacterium was transmitted from the carrier to recipient fish producing a lower intestinal carrier state but no deaths. Examination of experimentally infected fish to determine the number of carriers among the survivors indicated that the frequency varied as a function of time following infection. When immunized fish, were challenged with Y. ruckeri they became temporary carriers of the bacterium for up to 3 days; but were not able to transmit the infection to healthy recipient fish.

Notes: Book reviewed in this article: Diversity and Adaptation in Fish Behaviour. By M. H. A. Keenleyside. Exotic Species in Mariculture. By R. Mann. Developments in Marine Biology. Vol. 1. Toxic Dinoflagellate Blooms. Ed. by D. L. Taylor and H. H. Seliger Phytoplankton and the Fish Kills in Loch Striven. Ed by P. Tett.

Notes: Abstract. Atkinsiella hamanaensis sp. nov. a marine mastigomycete isolated from ova of the mangrove crab, Scylla serrata (Forsskål), is described and illustrated. The fungus grew over a temperature range of 15–32°C, with an optimum of 29–32°C. Its growth was observed in peptone-yeast extract glucose broth containing 1–5% NaCl, with optimum growth at 2–3% NaCl concentration. At 6% or more NaCl concentration, growth was inhibited. Its pH tolerance ranged from 4 to 9.

Notes: Abstract. Flagellates infesting the gills of freshwater fish are reviewed and Cryptobia branchialis Nie is differentiated from them. Gill filaments of two species of fish heavily infested with C. branchialis were examined with the transmission electron microscope. The flagellates are attached to the surface of the gill epithelium by their recurrent flagella. A prominent ridge on the flagellar membrane contacts the host cell membrane, forming a zone of gap junction and leaving a space of about 10 nm between the two membranes. The flagella do not penetrate into the epithelial cells. No other modifications of the cell membrane could be detected and the host cell reveals no signs of damage. Assumptions on the pathogenicity of C. branchialis are discussed in view of ultrastructural findings, which suggest that this flagellate is non-pathogenic and ectocommensal.