Abstract
The mouse major histocompatibility complex is composed of several genes arranged into the K, D, Qa, and Tla regions. The D region of the BALB/c mouse includes genes D2 d, D3 d, and D4 d, in addition to H-2D dand H-2L d. We have determined the DNA sequence of the D2 dgene and compared it with the known sequences of several class I genes. The exon/intron structure of the D2 dgene is similar to other class I genes. It also contains similar 5′ regulatory elements. A frameshift occurs in exon seven, resulting in a gene product with a truncated cytoplasmic tail. To examine the surface expression of the D2d molecule, we generated an exon-shuffled construct containing the promoter and exons 1–3, encoding the signal peptide, α1, and α2 external domains of the D2 dgene linked to exons 4–8, encoding the α3, transmembrane and cytoplasmic domains, of the H-2D dgene. The construct was transfected into mouse L cells, and a protein was detected at the cell surface by a monoclonal antibody (mAb) specific for the α3 domain of H-2Dd, as well as by other class I-specific mAbs. Although D2d is expressed at low levels, it may be a functional class I gene that most probably evolved from a Qa region gene.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Archibald, A. L., Thompson, N. A., and Kvist, S.: A single nucleotide difference at the 3′ end of an intron causes differential splicing of two histocompatibility genes. EMBO J 5: 957–965, 1986
Arnold, B., Burgert, H.-G., Archibald, A. L., and Kvist, S.: Complete nucleotide sequence of the murine H-2K kgene. Comparison of three H-2K locus alleles. Nucleic Acids Res 12: 9473–9487, 1984
Bjorkman, P. J., Saper, M. A., Samraoui, B.,Bennet, W. S., Strominger, J. L., and Wiley, D. C.: Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329: 506–518, 1987
Bregegere, F.: A directional process of gene conversion is expected to yield dynamic polymorphism associated with stability of alternative alleles in class I histocompatibility antigens gene family. Biochemie 65: 229–237, 1983
Chen, E. Y. and Seeburg, P. H.: Supercoil sequencing: a fast simple method for sequencing plasmid DNA. DNA 4: 165–170, 1985
Duran, L. W. and Pease, L. R.: Tracing the evolution of H-2 D region genes using sequences associated with a repetitive element. J Immunol 141: 295–301, 1988
Efstratiadis, A., Posakony, J. W., Maniatis, T., Lawn, R. M., O'Connell, C., Spritz, R. A., DeRiel, J. K., Forget, B. G., Weissman, S. M., Slightom, J. L.., Blechl, A. E., Smithies, O., Baralle, F. E., Shoulders, C. C., and Proudfoot, N. J.: The structure and evolution of the human β-globin gene family. Cell 21: 653–668, 1980
Goodenow, R. S., McMillan, M., Nicolson, M., Sher, B. T., Eakle, K., Davidson, N., and Hood, L.: Identification of the class I genes of the mouse major histocompatibility complex by DNA-mediated gene transfer. Nature 300: 231–237, 1982
Israel, A., Kimura, A., Fournier, A., Fellous, M., and Kourilsky, P.: Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene. Nature 322: 743–746, 1986
Jaulin, C., Perrin, A., Abastado, J.-P., Dumas, B., Papamatheakis, J., and Kourilsky, P.: Polymorphism in mouse and human class I H-2 and HLA genes is not the result of random independent point mutations. Immunogenetics 22: 453–470, 1985
Kimura, A., Israel, A., Bail, O. L., and Kourilsky, P.: Detailed analysis of the mouse H-2k bpromoter: enhancer-like sequences and their role in the regulation of class I gene expression. Cell 44: 261–272, 1986
Klein, J. and Figueroa, F.: The evolution of class I MHC genes. Immunol Today 7: 41–44, 1986
Kozak, M.: Compilation and analysis of sequences upstream from the translational start site in eukaryotic genes. Nucleic Acids Res 12: 857–872, 1984
Kvist, S., Roberts, L., and Dobberstein, B.: Mouse histocompatibility, genes: structure and organisation of K d. EMBO J 12: 245–254, 1983
Maxam, A. M. and Gilbert, W.: Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol 65: 499–560, 1980
McCluskey, J., Boyd, L. F., Maloy, W. L., Coligan, J. E., and Margulies, D. H.: Alternative processing of H-2Dd pre-mRNAs results in membrane expression of differentially phosphorylated protein products. EMBO J 5: 2477–2483, 1986
Melor, A. L., Weiss, E. H., Ramachandran, K., and Flavell, R. A.: A potential donor for the bm1 gene conversion event in the C57BL mouse. Nature 306: 792–795, 1983
Miyazaki, J.-I., Appella, E., and Ozato, K.: Negative regulation of the major histocompatibility class I gene in undifferentiated embryonal carcinoma cells. Proc Natl Acad Sci USA 83: 9537–9541, 1986
Moore, K. W., Sher, B. T., Sun, Y. H., Eakle, K. A., and Hood, L.: DNA sequence of a gene encoding a BALB/c mouse L dtransplantation antigen. Science 215: 679–682, 1982
Mount, S. M.: A catalogue of splice junction sequences. Nucleic Acids Res 10: 459–472, 1982
Murre, C., Choi, E., Weis, J., Seidman, J. G., Ozato, K., Liu, L., Burakoff, S. J., and Reiss, C. S.: Dissection of serological and cytotolytic T lymphocyte epitopes on murine major histocompatibility antigens by a recombinant H-2 gene separating the first two external domains. J Exp Med 160: 167–178, 1984
Proudfoot, N. J. and Brownlee, G. G.: 3′ non-coding region sequences in eukaryotic messenger RNA. Nature 263: 211–214, 1976
Sharrow, S. O., Flaherty, L., and Sachs, D.: Serologic cross-reactivity between class I MHC molecules and H-2-linked differentiation antigens as detected by monoclonal antibodies. J Exp Med 159: 21–40, 1984
Sher, B. T., Nairn, R., Coligan, J. E., and Hood, L. E.: DNA sequence of the H-2D d transplantation antigen gene. Proc Natl Acad Sci USA 82: 1175–1179, 1985
Steinmetz, M., Moore, K. W., Frefnger, J. G., Sher, B. T., Shen, F.W., Boyse, E. A., and Hood, L.: A pseudogene homologous to mouse transplantation antigens: transplantation antigens are encoded by eight exons that correlate with protein domains. Cell 25: 683–692, 1981
Steinmetz, M., Winoto, A., Minard, K., and Hood, L.: Clusters of genes encoding mouse transplantation antigens. Cell 28: 489–498, 1982
Stephan, D., Sun, H., Lindahl, K. F., Meyer, E., Hämmerling, G., Hood, L., and Steinmetz, M.: Organization and evolution of D region class I genes in the mouse major bistocompatibility complex. J Exp Med 163: 1227–1244, 1986
Straus, D. S., Stroynowski, I., Schiffer, S. G., and Hood, L.: Expression of hybrid class I genes of the major histocompatibility complex in mouse L cells. Proc Natl Acad Sci USA 82: 6245–6249, 1985
Strauss, E. C., Kobori, J. A., Sui, G., and Hood, L. E.: Specificprimer-directed DNA sequencing. Anal Biochem 154: 353–360, 1986
Townsend, A. R. M., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith, D., and McMichael, A. J.: The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44: 959–968, 1986
Vogel, J., Kress, M., Khoury, G., and Jay, G.: A transcriptional enhancer and interferon-responsive sequence in major histocompatibility complex. Mol Cell Biol 6: 3550–3554, 1986
Watts, S., Vogel, J. M., Harriman, W. D., Itoh, T., Stauss, H., and Goodenow, R. S.: DNA sequence analysis of the C3H H-2K kand H-2D kloci: evolutionary relationships to H-2 genes from four other mouse strains. J Immunol 139: 3878–3885, 1987
Zuniga, M. C., Malissen, B., McMillan, M., Brayton, P. R., Clark, S. S., Forman, J., and Hood, L.: Expression and function of transplantation antigens with altered or deleted cytoplasmic domains. Cell 34: 535–544, 1983
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hedley, M.L., Hunt, S.W., Brorson, K.A. et al. Analysis of D2 d: a D-region class I gene. Immunogenetics 29, 359–365 (1989). https://doi.org/10.1007/BF00375863
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00375863