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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 38 (1993), S. 141-145 
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Nucleotide sequence analysis of rhesus macaque major histocompatibility complex class I cDNAs allowed the identification of the orthologue of HLA-F, designated Mamu-F. Comparison of Mamu-F with earlier published human and chimpanzee orthologues demonstrated that these sequences share a high degree of similarity, both at the nucleotide and amino acid level, whereas a New World monkey (cotton-top tamarin) equivalent is more distantly related. Exon 7, encoding one of the cytoplasmatic domains, is absent for all primate Mhc-F cDNA sequences analyzed so far. In contrast to the human, chimpanzee, and rhesus macaque equivalents, the cotton-top tamarin Saoe-F gene seems to have accumulated far more nonsynomynous than synonymous differences.
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  • 2
    ISSN: 1432-1211
    Keywords: HLA DQA1 HLA DQB1 HERV LTR Evolution MHC Primates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Long terminal repeats (LTRs) are common retrovirus-related sequences spread throughout the human genome. We previously reported the human-specific integration of one LTR (DQLTR3) located 15 kb upstream of HLA DQB1. To elucidate the contribution of retroviral sequences to the variability and phylogenetic background of HLA DQB1 we investigated another LTR (DQLTR13), located 1.3 kb upstream of HLA DQB1, in German families, great apes, and Old World monkeys. Within German families, DQLTR13 presence was strongly linked to HLA DQB1*0302, *0303, and *0402 haplotypes. All other haplotypes had a low frequency or were devoid of DQLTR13. Phylogenetic analysis of DQLTR13 and adjacent nucleotide sequences in humans and nonhuman primates revealed a high degree of similarity and recent origin of HLA DQB1*0302, *0303, and *0402. Nevertheless, two lineages leading to DQB1*0301 and *0302 were generated by an ancient split of a DQB1*0301, *0302 progenitor. A third lineage consisting of DQB1*05/*06-related sequences may have evolved from the DQB1*0302 lineage, and a DQB1*0201-related sequence shared common ancestry with DQB1*0301. Among the human haplotypes, HLA DQB1*0201 and *0301 are linked to two different DQA1 alleles. Based on the small genetic distance of DQLTR13 as well as the adjacent sequences on these haplotypes, we suggest that a recent recombination is responsible for these associations. In the analysis of nonhuman primate species, we detected DQLTR13 in two lowland gorillas, dating the integration at at least 8 million years ago. We therefore conclude that noncoding sequences up to 1.3 kb upstream of DQB1 provide novel insight into the generation of MHC gene diversity.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Immunogenetics 25 (1987), S. 305-312 
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract HLA-DQ molecules were isolated from a panel of HLA-DR-DQ homozygous cell lines, partially of consanguineous origin, derived by the use of monoclonal antibody SPV-L3, and subsequently analyzed by gel electrophoretic techniques. It is demonstrated that both the DQ alpha and beta chain exhibit an extensive isoelectric point polymorphism. Within a panel of 29 B-cell lines tested, at least 5 distinct alpha and 6 distinct DQ beta chain gene products were observed. Of the 30 theoretically possible DQ alpha-beta dimers, only 10 could be identified within the panel: 5 different dimers are associated with the DQw1 allospecificity; HLA-DQw2 and -DQw3 are associated with 2 types of dimers, whereas another DQ alpha-beta combination was expressed by a cell line with a so-called DQ-blank specificity. The relation between the specificities 2B3 and TA10 appeared to be complicated as far as DQ beta chain isoelectric point differences are concerned: monoclonal antibody IIB3 seems to be reactive with four distinct DQ beta chain alleles whereas monoclonal antibody TA10 only reacted with one type of DQ beta chain. These results suggest that the polymorphic DQ alpha and beta chains may both contribute to the definition of the HLA-DQ allospecificity. A particular DQ beta chain was present in two types of HLA-DQw1 molecules, as well as in one type of HLA-DQw2 and -DQw3 (2133 positive) molecule, and formed dimers with electrophoretic distinct DQ alpha chains. On the other hand, HLA-DQw2 molecules isolated from HLA-DR3-positive cells and one type of HLA-DQw3 (TA10 positive) molecule were found to be constructed of identical alpha chains but appeared to differ in the composition of their DQ beta chain gene products. The implications of these findings will be discussed.
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  • 4
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract HLA-DR molecules were isolated from HLA-DR3, −5, and −w6 positive homozygous B-cell lines by immunoprecipitation with monoclonal antibodies and analyzed by gel electrophoretic techniques. DNA isolated from the same cell lines was digested with the restriction enzyme Taq I and hybridized with a DR beta full-length cDNA probe. We demonstrated that certain DR βI alleles are found in combination with different DR βIII alleles as defined by Southern blotting, protein chemistry, a functional assay using purified protein derivative-specific T-cell lines, and, in one case, also alloreactive T-cell reagents. Our results indicate that within the family of HLA-DRw52-associated haplotypes DR beta chain genes may have been transferred from one haplotype to another. The implications of these findings are discussed.
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  • 5
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract AB T-cell receptors (TCR) that recognize major histocompatibility complex (MHC)/peptide antigen complexes regulate humoral and cellular arms of the adaptive immune response. Antigen binding sites of MHC and immunoglobulin heavy chain variable regions(Igh-V) are subject to diversity enhancing selection. We sought to establish whether positive Darwinian selection has driven diversity of TCRBV chains in the primate lineage by sequencing rearranged TCR from rhesus monkeys and chimpanzees and comparing them with those of humans. Rates of synonymous (silent) and nonsynonymous (replacement) substitutions indicate selection against amino acid replacements in TCRBV frameworks, and relaxation of these constraints in putative MHC/peptide contact sites. The lack of positive selection for variability in likely ligand contact sites suggests that mechanisms generating somatic diversity in TCR junctional regions have relaxed the pressure for selection of variability in the TCR V region encoded in the germline.
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  • 7
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Allelic diversity at the major histocompatibility complex class II DP locus of rhesus macaques was studied by sequencing exon 2 of Mamu-DPA1 and -DPB1 genes. The Mamu-DPA1 gene is apparently invariant, whereas the Mamu-DPB1 locus displays polymorphism. Here we report the characterization of 1 Mamu-DPA1 and 13 Mamu-DPB1 alleles which were compared with other available primate Mhc-DPA1 and -DPB1 sequences. As compared with Mhc-DRB and -DQB1, most codons for the contact residues in the antigen binding site of the primate Mhc-DPB1 gene have a relatively low degree of variation in encoding various types of amino acids. In contrast to Mhc-DRB and -DQB, the HLA- and Mamu-DPB1 sequences cluster in a species-specific manner in phylogenetic trees. Mhc-DPB1 polymorphisms, however, are inherited in a transspecies mode of evolution, as is demonstrated by the sharing of lineage members between closely related macaque species. The data demonstrate that the transspecies character of Mhc-DPB1 polymorphism was retained over much shorter periods of time as compared with its sister class II loci, Mhc-DQ and -DR.
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  • 8
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The human and chimpanzee T-cell receptor gamma-delta (TCR γδ) bearing cells represent a minor subset (3–8%) of T lymphocytes. In the periphery, the TCR γδ population has a restricted combinatorial repertoire. The TCRD-V1 and-V2 gene products are expressed in a mutually exclusive fashion, whereas, the TCRD-V2 and the TCRG-V9 encoded proteins show, in general, a coordinated expression. Restriction fragment length polymorphism analysis showed conservation of the restriction sites that identify the TCRG-V9 and TCRD-V2 rearrangements. The human TCRG-V9 locus has two alleles, TCRG-V9A1 and TCRG-V9A2 differing at codon position 31. The chimpanzee TCRG-V9 gene product differs from the products of the human TCRG-V9A1 and TCRG-V9A2 allele by two and three amino acid replacements, respectively. The human and the chimpanzee TCRG-V9-TCRD-V2 lymphocytes show a similar specific proliferative and cytolytic response to human Daudi Burkitt's lymphoma cells. Therefore, the amino acid replacements found in the chimpanzee TCRG-V9 gene product do not change the superantigen specificity across this species barrier.
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  • 9
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Rhesus macaques represent important animal models for biomedical research. The ability to identify macaque major histocompatibility complex (Mhc) alleles is crucial for fully understanding these models of autoimmune and infectious disease. Here we describe a rapid and unambiguous way to distinguish DRB alleles in the rhesus macaque using the polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and direct sequencing. The highly variable second exon of Mamu-DRB alleles was amplified using generic DRB primers and alleles were separated by DGGE. DNA was then reamplified from plugs removed from the gel and alleles were determined using fluorescent-based sequencing. Validity of this typing procedure was confirmed by identification of all DRB alleles for three macaques previously characterized by cloning and sequencing techniques. Importantly, our analysis revealed DRB alleles not previously identified in the three reference animals. Using this technique, we identified 40 alleles in fifteen unrelated macaques. On the basis of phylogenetic tree analyses, 14 new DRB alleles were assigned to 10 different Mhc-DRB lineages. Interestingly, two of the new DRB6 lineages had previously been identified in prosimians and pigtailed macaques. Whereas traditional DRB typing methods provide limited information, our new technique provides a simple and relatively rapid way of identifying DRB alleles for tissue typing, determining individual identification and studies of disease association and susceptibility. This new technique should also contribute to ongoing studies of Mhc function and evolution in many different species of nonhuman primates.
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  • 10
    ISSN: 1432-1211
    Keywords: Key words T-cell receptor ; Variable region ; Genetic polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The functional relevance of the majority of human T-cell receptor A and B variable region gene polymorphisms is controversial. Studies of human and nonhuman primate major histocompatibility complex (MHC) class I and II polymorphisms show that allelic lineages predate human speciation and indicate that selection favors the long-term maintenance of these advantageous mutations. We investigated at the DNA level whether 15 human TCRA and B polymorphisms exist in contemporary chimpanzee populations. Polymorphisms consisted of variable region replacements, a recombination signal sequence base change, and silent mutations. With one exception, none of these human TCR polymorphisms were observed in contemporary chimpanzees. Investigation of the same polymorphisms in a range of other nonhuman primates showed little evidence of the existence of human polymorphism prespeciation. Chimpanzee TCRAV and BV regions were however polymorphic for variation so far not observed in human groups. Levels of mitochondrial and nuclear DNA sequence variation in contemporary chimpanzees suggest that population bottlenecks have not been a feature of chimpanzee evolution and it is therefore probable that most human TCR polymorphisms have evolved in the estimated five million years since the speciation of human and chimpanzees. Thus, over the evolutionary time period studied, ancient TCRA and B polymorphisms have not been maintained by selection to the same degree as postulated for MHC polymorphisms.
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