H-2 Antigens pp 169-176 | Cite as

The Analysis of H-2 Mutants: Molecular Genetics and Structure/Function Relationships

  • Jan Geliebter
  • Richard A. Zeff
  • Rita Spathis
  • Gertrude Pfaffenbach
  • Mayumi Nakagawa
  • Brigid McCue
  • Hiroshi Mashimo
  • Krishna Kesari
  • Silvio Hemmi
  • Kim Hasenkrug
  • Francescopaolo Borriello
  • P. Ajit Kumar
  • Stanley G. Nathenson
Part of the NATO ASI Series book series (NSSA, volume 144)

Abstract

The class I genes of the murine major histocompatibility complex are located in four regions (K, D, Qa, Tla) along chromosome 17. The K and D regions contain the genes encoding the classical H-2 transplantation antigens (K, D, L). Alleles of each of the K, D and L loci exhibit substantial sequence diversity (1–3). Further, H-2 loci are highly polymorphic, with over 100 alleles identified per locus (3). The high sequence diversity and polymorphism of H-2 genes are thought to play a role in the function of their products as antigen presenting molecules, thus enabling a population to respond to many different pathogens. In contrast, Qa and Tla region loci are much less polymorphic and alleles of each locus appear to be much more conserved (4,5). Qa and Tla gene products have a limited tissue distribution and their function is unknown.

Keywords

Major Histocompatibility Complex Donor Gene Associative Recognition Gene Conversion Event High Sequence Diversity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Steinmetz, M., and Hood, L., Genes of the major histocompatibility complex in mouse and man, Science 222: 727 (1983).PubMedCrossRefGoogle Scholar
  2. 2.
    Kimball, E. S., and Coligan, J. E., Structure of class I major histocompatibility antigens, Contemp. Topics Molec. Immunol. 9: 1 (1983).Google Scholar
  3. 3.
    Klein, J., and Figueroa, F., Evolution of the major histocompatibility complex, Critical Reviews in Immunology 6: 295 (1986).PubMedGoogle Scholar
  4. 4.
    Flavell, R. A., Allen, H., Burkly, L. C., Sherman, D. H., Waneck, G. L., and Widera, G., Molecular biology of the H-2 histocompatibility complex, Science 233: 437 (1986).PubMedCrossRefGoogle Scholar
  5. 5.
    Pontarotti, P., Mashimo, H., Zeff, R. A., Fisher, D., Hood, L., Mellor, A., Flavell, R. A., and Nathenson, S. G., Conservation vs. diversity in the class I genes of the major histocompatibility complex: Sequence analysis of the Tlaa gene and comparison with a TlaL gene, Proc. Natl. Acad. Sci. USA 83: 1782 (1985).CrossRefGoogle Scholar
  6. 6.
    Nairn, R., Yamaga, K., and Nathenson, S.G., Biochemistry of the gene products from murine MHC mutants, Ann. Rev. Genet. 14: 241 (1980).PubMedCrossRefGoogle Scholar
  7. 7.
    Weiss, E. H., Mellor, A., Golden, L., Fahner, K., Simpson, E., Hurst, J., and Flavell, R. A., The structure of a mutant H-2 gene suggests that the generation of polymorphism in H-2 genes may occur by gene conversion-like events, Nature 301: 671 (1983)PubMedCrossRefGoogle Scholar
  8. 8.
    Schulze, D. H., Pease, L. R., Geier, S. S., Reyes, A. A., Sarmiento, L. A., Wallace, R. B., and Nathenson, S. G., Comparison of the cloned H-2Kbml variant gene with the H-2Ku gene shows a cluster of seven nucleotide differences, Proc. Natl. Acad. Sci. USA 80: 2007 (1983).PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Geliebter, J., Zeff, R. A., Melvold, R. W., and Nathenson, S. G., Mitotic recombination in germ cells generated twobmC mutgn s determined to be identical by RNA sequence analysis: K and K. Proc. Natl. Acad. Sci USA 83: 3371 (1986).PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Geliebter, J., and Nathenson, S. G., Micro-recombinations generate sequence diversity in thee m r e major hh stocompatibility complex: Analyses of the Kum’, Kbm4 Kum’’, and Kbmll mutants, submitted.Google Scholar
  11. 11.
    Pease, L. R., Schulze, D. H., Pfaffenbach, G. M., and Nathenson, S. G., Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex, Proc. Natl. Acad. Sci. USA 80: 242 (1983).PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Melief, C. J. M., de Waal, L. P., van der Meulen, M. Y., Melvold, R. W., and Kohn, H. I., Fine specificity of alloimmune cytotoxic T lymphocytes directed against H-2K. A study of Kb mutants, J. Exp. Med. 151: 993 (1980).PubMedCrossRefGoogle Scholar
  13. 13.
    Sherman, L. A., Recognition of conformational determinants on H-2 by cytolytic T lymphocytes, Nature 997: 511 (1982).CrossRefGoogle Scholar
  14. 14.
    Clark, S. S., Geier, S., Nathenson, S. G., and Forman, J., Analysis of associative recognition determinants on class I H-2Kb mutant molecules, Immunoqenetics 22: 391 (1985).CrossRefGoogle Scholar
  15. 15.
    Blanden, R. V., Dunlop, M. B. C., Doherty, P. C., Kohn, H. I. and McKenzie, I. F. C., Effects of four H-2K mutations on virus-induced antigens recognized by cytotoxic T cells, Immunoqenetics 3: 541 (1976).CrossRefGoogle Scholar
  16. 16.
    Yamaga, K. M., Pfaffenbach, G. M., Pease, L. R., McGovern, D., Nisizawa, T., Melvold, R. W., Kohn, H. I., and Nathenson, S. G., Biochemical studies of H-2K antigens from a group bm5 related mutants. I. Identification of a shared mutation in B6-H-2 and B6-H-2“1”, Immunogenetics 17: 19 (1983).PubMedCrossRefGoogle Scholar
  17. 17.
    Yamaga, K. M., Pfaffenbach, G. M., Pease, L. R., McGovern, D., Nisizawa, T., Melvold, R. W., Kohn, H. I., and Nathenson, S. G., Biochemical studies of H-2K antigens from a group of r,elated mutants. II. Ide tification of a shared mutation in B6-H-2bm, 86.C-H-25m, B6.C-H-2um9 (1983).Google Scholar
  18. 18.
    Evans, G. A., Margulies, D. H., Camerini-Otero, R. D., Ozato, K., and Seidman, J. G., Structure and expression of a mouse major histocompatibility antigen gene, H-2L, Proc. Natl. Acad. Sci. USA 79: 1994 (1982).CrossRefGoogle Scholar
  19. 19.
    Steinmetz, M., Frelinger, J. G., Fisher, D., Hunkapiller, T., Pereira, D., Weissman, S. M., Uehara, H., Nathenson, S. G., and Hood, L., Three cDNA clones encoding mouse transplantation antigens: Homology to immunoglobulin genes, Cell 24: 125 (1981).PubMedCrossRefGoogle Scholar
  20. 20.
    Pease, L. R., Nathenson, S. G., and Leinwand, L. A., Mapping class I gene sequences in the major histocompatibility complex, Nature 298: 382 (1982).PubMedCrossRefGoogle Scholar
  21. 21.
    Weiss, E. H., Golden, L., Fahrner, K., Mellor, A. L., Devlin, J. J., Bullman, H., Tiddens, H., Bud, H., and Flavell, R. A., Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse, Nature 310: 650 (1984).PubMedCrossRefGoogle Scholar
  22. 22.
    Steinmetz, M., Winoto, A., Minard, K., and Hood, L., Clusters of genes encoding mouse transplantation antigens, Cell 28: 489 (1982).PubMedCrossRefGoogle Scholar
  23. 23.
    Mellor, A. L., Weiss, E. H., Ramachandran, K., and Flavell, R. A., A potential donor gene for the ball gene conversion event in the C57BL mouse, Nature 306: 792 (1983).PubMedCrossRefGoogle Scholar
  24. 24.
    Mcjntx re, K. R., and Seidman, J. G., Nucleotide sequence of mutant I- nmicgene is evidence for genetic exchange between mouse immune response genes, Nature 308: 551 (1984).CrossRefGoogle Scholar
  25. 25.
    Wideta, G., and Flavell, R. A., The nucleotide sequence of the murine I-EB immune response gene: Evidence for gene conversion events in class II genes of the major histocompatibility complex, EMBO J. 3: 1221 (1984).Google Scholar
  26. 26.
    Sun, Y. H., Goodenow, R. S., and Hood, L., Molecular basis of the dm1 mutation in the major histocompatibility complex of the mouse: A D/L hybrid gene, J. Exp. Med. 162: 1588, 1985.PubMedCrossRefGoogle Scholar
  27. 27.
    Weiss, E. H., Golden, L., Zakut, R., Mellor, A., Fahrner, K., Kvist, S., and Flavell, R. A., The DNA sequence of the H-2Ku gene: Evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibility antigens, EMBO J. 2: 453 (1983).PubMedPubMedCentralGoogle Scholar
  28. 28.
    Kvist, S., Roberts, L., and Dobberstein, B., Mouse histocompatibility genes: Structure and organization of a Kd gene, EMBO J. 2: 245 (1983).PubMedPubMedCentralGoogle Scholar
  29. 29.
    Fisher, D. A., Hunt III, S. W., and Hood, L., The structure of a gene encoding a Murine Thymus Leukemia antigen and the organization of Tla genes in the BALB/c mouse, J. Exp. Med. 162: 528 (1985).PubMedCrossRefGoogle Scholar
  30. 30.
    O’Neill, A. E., Reid, K., Garberi, J. C., Karl, M., and Flaherty, L., Extensive deletions in the Q region of the mouse major histocompatibility complex, Immunogenetics 24: 368 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Jan Geliebter
    • 1
  • Richard A. Zeff
    • 1
  • Rita Spathis
    • 1
  • Gertrude Pfaffenbach
    • 1
  • Mayumi Nakagawa
    • 1
  • Brigid McCue
    • 1
  • Hiroshi Mashimo
    • 1
  • Krishna Kesari
    • 1
  • Silvio Hemmi
    • 1
  • Kim Hasenkrug
    • 1
  • Francescopaolo Borriello
    • 1
  • P. Ajit Kumar
    • 1
  • Stanley G. Nathenson
    • 1
  1. 1.Departments of Cell Biology and Microbiology and ImmunologyAlbert Einstein College of MedicineBronxUSA

Personalised recommendations