Structural and Functional Studies of Mouse Class II Genes

  • M. Steinmetz

Abstract

This review summarizes our current knowledge about the organization, structure, expression, and evolution of the class II genes in the major histocompatibility complex (MHC) of the mouse. Class II genes code for highly polymorphic cell surface molecules, called class II antigens or Ia antigens. The mouse class II antigens are the counterparts to the human HLA-DP, DQ, and DR antigens (previously called SB, DC/DS/MB, and DR, respectively) which are encoded in the D region of the HLA complex. Class II molecules play an important role in the generation of immune responses because they are involved in the recognition of foreign antigens by regulatory T cells (for recent reviews see [28, 65]).

Keywords

Lymphoma Leukemia Recombination Cysteine Electrophoresis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Adorini L, Palmieri G, Sette A, Appella E, Doria G (1985) Expression of T cell receptor β chain gene products by a mouse monoclonal antigen-specific suppressor T cell line. Curr Top Microbiol Immunol (in press)Google Scholar
  2. 2.
    Allen H, Wraith D, Pala P, Askonas B, Flavell RA (1984) Domain interactions of H-2 class I antigens alter cytotoxic T cell recognition sites. Nature 309:279–281PubMedCrossRefGoogle Scholar
  3. 3.
    Arden B, Klein J (1982) Biochemical comparison of major histocompatibility complex molecules from different subspecies of Mus musculus: evidence for trans-specific evolution of alleles. Proc Natl Acad Sci USA 79:2342–2346PubMedCrossRefGoogle Scholar
  4. 4.
    Arnold B, Burgert HG, Hamann U, Hämmerling G, Kees U, Kvist S (1984) Cytolytic T cells recognize the two amino-terminal domains of H-2 K antigens in tandem in influenza A infected cells. Cell 38:79–87PubMedCrossRefGoogle Scholar
  5. 5.
    Auffray C, Lillie JW, Arnot D, Grossberger D, Kappes D, Strominger JL (1984) Isotypic and allotypic variation of human class II histocompatibility antigen α-chain genes. Nature 308:327–333PubMedCrossRefGoogle Scholar
  6. 6.
    Ben-Nun A, Glimcher LH, Weis J, Seidman JG (1984) Functional expression of a cloned I-Aβ k gene in B-lymphoma cells. Science 223:825–828PubMedCrossRefGoogle Scholar
  7. 7.
    Benoist CO, Mathis DJ, Kanter MR, Williams VE, McDevitt HO (1983) The murine la α chains, Eα and Aα, show a surprising degree of sequence homology. Proc Natl Acad Sci USA 80:534–538PubMedCrossRefGoogle Scholar
  8. 8.
    Benoist CO, Mathis DJ, Kanter MR, Williams II VE, McDevitt HO (1983) Regions of allelic hypervariability in the murine Aα immune response gene. Cell 34:169–177PubMedCrossRefGoogle Scholar
  9. 9.
    Bodmer J, Bodmer W (1984) Histocompatibility 1984. Immunol Today 5:251–254CrossRefGoogle Scholar
  10. 10.
    Braunstein N, Germain R (1985) The murine E β2 gene: structure, sequence and expression. In: Streilein et al. (eds) Advances in gene technology: molecular biology of the immune system. Cambridge University Press, Cambridge, p 119–120Google Scholar
  11. 11.
    Collins T, Korman AJ, Wake CT, Boss JM, Kappes DJ, Fiers W, Ault KA, Gimbrone MA, Strominger JL, Pober JS (1984) Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. Proc Natl Acad Sci USA 81:4917–4921PubMedCrossRefGoogle Scholar
  12. 12.
    Dembić Z, Singer PA, Klein J (1984) E°: a history of a mutation. EMBO J 3:1647–1654PubMedGoogle Scholar
  13. 13.
    Dembić Z, Ayane M, Klein J, Steinmetz M, Benoist CO, Mathis DJ (1985) Inbred and wild mice carry identical deletions in their Eα MHC genes. EMBO J 4:127–131PubMedGoogle Scholar
  14. 14.
    Denaro M, Hammerling U, Rask L, Peterson PA (1984) The Eβ b gene may have acted as the donor gene in a gene conversion like event generating the Aβ bm12 mutant. EMBO J 9:2029–2032Google Scholar
  15. 15.
    Falkner FG, Zachau HG (1984) Correct transcription of an immunoglobulin K gene requires an upstream fragment containing conserved sequence elements. Nature 310:71–74PubMedCrossRefGoogle Scholar
  16. 16.
    Folsom V, Gold DP, White J, Marrack P, Kappler J, Tonegawa S (1984) Functional and inducible expression of a transfected murine class II major histocompatibility complex gene. Proc Natl Acad Sci USA 81:2045–2049PubMedCrossRefGoogle Scholar
  17. 17.
    Germain RN, Norcross MA, Margulies DH (1983) Functional expression of a transfected murine class II MHC gene. Nature 306:190–194PubMedCrossRefGoogle Scholar
  18. 18.
    Germain RN, Ashwell JD, Lechler RI, Margulies DH, Nickerson KM, Suzuki G, Tou JYL (1985) Exon-shuffling maps control of antibody and T cell recognition sites to the NH2 terminal domain of Aβ,. Proc Natl Acad Sci USA 82:2940–2944PubMedCrossRefGoogle Scholar
  19. 19.
    Gillies SD, Folsom V, Tonegawa S (1984) Cell type-specific enhancer element associated with a mouse MHC gene, Eβ. Nature 310:594–597PubMedCrossRefGoogle Scholar
  20. 20.
    Gustafsson K, Wiman K, Emmoth E, Larhammar D, Böhme J, Hyldig-Nielsen JJ, Ronne H, Peterson PA, Rask L (1984) Mutations and selection in the generation of class II histocompatibility antigen polymorphism. EMBO J 3:1656–1661Google Scholar
  21. 21.
    Hayes CE, Bach FH (1980) I-N, a newly described H-21 subregion between K and I-A. J Exp Med 151:481–485PubMedCrossRefGoogle Scholar
  22. 22.
    Hayes CE, Klyczek KK (1985) The I-J glycoprotein: Genetic control, biochemistry, and function. Immunol Rev 83:41–59PubMedCrossRefGoogle Scholar
  23. 23.
    Hayes CE, Klyczek KK, Krum DP, Whitcomb RM, Hullett DA, Cantor H (1984) Chromosome 4 Jt gene controls murine T cell surface I-J expression. Science 223:559–563PubMedCrossRefGoogle Scholar
  24. 24.
    Hedrick SM, Germain RN, Bevan MJ, Dorf M, Engel I, Fink P, Gascoigne N, Heber-Katz E, Kapp J, Kaufmann Y, Kaye J, Melchers F, Pierce C, Schwartz RH, Sorensen C, Taniguchi M, Davis MM (1985) Rearrangement and transcription of a T-cell receptor β-chain gene in different T-cell subsets. Proc Natl Acad Sci USA 82:531–535PubMedCrossRefGoogle Scholar
  25. 25.
    Hood L, Steinmetz M, Malissen B (1983) Genes of the major histocompatibility complex of the mouse. Ann Rev Immunol 1:529–568CrossRefGoogle Scholar
  26. 26.
    Hyldig-Nielsen JJ, Schenning L, Hammerling U, Widmark E, Heldin E, Lind P, Servenius B, Lund T, Flavell R, Lee JS, Trowsdale J, Schreier PH, Zablitzky F, Larhammar D, Peterson PA, Rask L (1983) The complete nucleotide sequence of the I-Eα d, immune response gene. Nucleic Acids Res 11:5055–5071PubMedCrossRefGoogle Scholar
  27. 27.
    Jones PP, Murphy DB, McDevitt HO (1981) Variable synthesis and expression of Eα and Ae (Eβ) la polypeptide chains in mice of different H-2 haplotypes. Immunoge-netics 12:321–337CrossRefGoogle Scholar
  28. 28.
    Kaufman JF, Auffray C, Korman A J, Shackelford DA, Strominger J (1984) The class II molecules of the human and murine major histocompatibility complex. Cell 36:1–13PubMedCrossRefGoogle Scholar
  29. 29.
    Kelly A, Trowsdale J (1985) Complete nucleotide sequence of a functional HLA-DPβ gene and the region between the DPβ1 and DPαl genes: comparison of the 5’ ends of HLA Class II genes. Nucleic Acids Res 13:1607–1621PubMedCrossRefGoogle Scholar
  30. 30.
    Klein J (1975) Biology of the mouse histocompatibility complex. Springer, Berlin Heidelberg New YorkGoogle Scholar
  31. 31.
    Klein J, Figueroa F (1981) Polymorphism of the mouse H-2 loci. Immunol Rev 60:23–57PubMedCrossRefGoogle Scholar
  32. 32.
    Klein J, Figueroa F, David CS (1983) H-2 haplo types, genes and antigens: second listing. Immunogenetics 17:553–596PubMedCrossRefGoogle Scholar
  33. 33.
    Kobori J A, Winoto A, McNicholas J, Hood L (1984) Molecular characterization of the recombination region of six murine major histocompatibility complex (MHC) I-region recombinants. J Mol Cell Immunol 1:125–131PubMedGoogle Scholar
  34. 34.
    Kronenberg M, Goverman J, Haars R, Malissen M, Kraig E, Phillips L, Delovitch T, Suciu-Foca N, Hood L (1985) Rearrangement and transcription of the β-chain genes of the cell antigen receptor in different types of murine lymphocytes. Nature 313:647- 653PubMedCrossRefGoogle Scholar
  35. 35.
    Kumagai Y, Okumura K, Tada T (1984) Photoaffinity labeled hap ten-binding T cell receptor on a suppressor T cell hybridoma. Mol Immunol 21:545–559PubMedCrossRefGoogle Scholar
  36. 36.
    Landais D, Matthes H, Benoist C, Mathis D (1985) A molecular basis for the Ia-2 and Ia-19 antigenic determinants. Proc Natl Acad Sci USA 82:2930–2934PubMedCrossRefGoogle Scholar
  37. 37.
    Larhammar D, Hammerling U, Denaro M, Lund T, Flavell RA, Rask L, Peterson PA (1983) Structure of the murine immune response I-Aβ locus: sequence of the I-Aβ gene and an adjacent β-chain second domain exon. Cell 34:179–188PubMedCrossRefGoogle Scholar
  38. 38.
    Larhammar D, Servenius B, Rask L, Peterson PA (1985) Characterization of an HLA-DR β pseudogene. Proc Natl Acad Sci USA 82:1475–1479PubMedCrossRefGoogle Scholar
  39. 39.
    Malissen B, Steinmetz M, McMillan M, Pierres M, Hood L (1983) Expression of I-Ak class II genes in mouse L cells after DNA-mediated gene transfer. Nature 305:440–443PubMedCrossRefGoogle Scholar
  40. 40.
    Malissen M, Hunkapiller T, Hood L (1983) Nucleotide sequence of a light chain gene of the mouse I-A subregion: Aβ d. Science 221:750–754PubMedCrossRefGoogle Scholar
  41. 41.
    Malissen B, Price MP, Goverman JM, McMillan M, White J, Kappler J, Marrack P, Pierres A, Pierres M, Hood L (1984) Gene transfer of H-2 class II genes: antigen presentation by mouse fibroblast and hamster B-cell lines. Cell 36:319–327PubMedCrossRefGoogle Scholar
  42. 42.
    Marche PN, Tykocinski ML, Max EE, Kindt TJ (1985) Structure of a functional rabbit class I MHC gene: similarity to human class I genes. Immunogenetics 21:71–82PubMedCrossRefGoogle Scholar
  43. 43.
    Mathis DJ, Benoist C, Williams VE, Kanter M, McDevitt HO (1983) Several mechanisms can account for defective Ea gene expression in different mouse haplotypes. Proc Natl Acad Sci USA 80:273–277PubMedCrossRefGoogle Scholar
  44. 44.
    Mathis DJ, Benoist CO, Williams II VE, Kanter MR, McDevitt HO (1983) The murine Eα immune response gene. Cell 32:745–754PubMedCrossRefGoogle Scholar
  45. 45.
    Mclntyre KR, Seidman JG (1984) Nucleotide sequence of mutant I-Aβ bm12 gene is evidence for genetic exchange between mouse immune response genes. Nature 308:551–553CrossRefGoogle Scholar
  46. 46.
    Mellor AL, Weiss EH, Ramachandran K, Flavell RA (1983) A potential donor gene for the bml gene conversion event in the C57BL mouse. Nature 306:792–795PubMedCrossRefGoogle Scholar
  47. 47.
    Mengle-Gaw L, Conner S, McDevitt HO, Fathman CG (1984) Gene conversion between murine class II major histocompatibility complex loci. J Exp Med 160:1184–1194PubMedCrossRefGoogle Scholar
  48. 48.
    Monaco J J, McDevitt HO (1982) Identification of a fourth class of proteins linked to the murine major histocompatibility complex. Proc Natl Sci USA 79:3001–3005CrossRefGoogle Scholar
  49. 49.
    Murphy DB (1981) Genetic fine structure of the H-2 gene complex. In: Dorf ME (ed) The role of the major histocompatibility complex in immunobiology. Garland STPM, New York, p 1–32Google Scholar
  50. 50.
    Murre C, Choi E, Weiss J, Seidman JG, Ozato K, Liu L, Burakoff SJ, Reiss CS (1984) Dissection of serologic and cytolytic T lymphocyte epitopes on murine major histocompatibility antigens by a recombinant H-2 gene separating the first two external domains. J Exp Med 160:167–178PubMedCrossRefGoogle Scholar
  51. 51.
    Nathenson SG, Geliebter J, Geier SS, Mashimo H, Hemmi S, Kumar A, McGovern D, Nakagawa M, Pfaffenbach G, Pontarotti P, Zeff R (1985) The study of H-2 major histocompatibility complex mutants reveals structure-function relationships and mechanisms of generation of diversity and polymorphism. In: Streilein et al. (eds) Advances in gene technology: molecular biology of the immune system. Cambridge University Press, Cambridge, p 37–40Google Scholar
  52. 52.
    Norcross MA, Bentley DM, Margulies DH, Germain RN (1984) Membrane la expression and antigen-presenting accessory cell function of L cells transfected with Class II major histocompatibility complex genes. J Exp Med 160:1316–1337PubMedCrossRefGoogle Scholar
  53. 53.
    Ozato K, Evans GA, Shykind B, Margulies DH, Seidman JG (1983) Hybrid H-2 histocompatibility gene products assign domains recognized by alloreactive T cells. Proc Natl Acad Sci USA 80:2040–2043PubMedCrossRefGoogle Scholar
  54. 54.
    Pober JS, Collins T, Gimbrone Jr MA, Cotran RS, Gitlin JD, Fiers W, Clayberger C, Krensky AM, Burakoff SJ, Reiss CS (1983) Lymphocytes recognize human vascular endothelial and dermal fibroblast la antigens induced by recombinant immune interferon. Nature 305:726–729PubMedCrossRefGoogle Scholar
  55. 55.
    Rabourdin-Combe C, Mach B (1983) Expression of HLA-DR antigens at the surface of mouse L cells co-transfected with cloned human genes. Nature 303:670–674PubMedCrossRefGoogle Scholar
  56. 56.
    Radding CM (1978) Genetic recombination: strand transfer and mismatch repair. Ann Rev Biochem 47:847–880PubMedCrossRefGoogle Scholar
  57. 57.
    Reiss CS, Evans GA, Margulies DH, Seidman JG, Burakoff SJ (1983) Allospecific and virus-specific cytolytic T lymphocytes are restricted to the N or CI domain of H-2 antigens expressed on L cells after DNA-mediated gene transfer. Proc Natl Acad Sci USA 80:2709–2712PubMedCrossRefGoogle Scholar
  58. 58.
    Rogers MJ, Germain RN, Hare J, Long E, Singer DS (1985) Comparison of MHC genes among distantly related members of the genus Mus. J Immunol 134:630–636PubMedGoogle Scholar
  59. 59.
    Rosa F, Fellous M (1984) The effect of gamma-interferon on MHC antigens. Immunol Today 5:261–262CrossRefGoogle Scholar
  60. 60.
    Royer HD, Bensussan A, Acuto O, Reinherz EL (1984) Functional isotypes are not encoded by the constant region genes of the β subunit of the T cell receptor for antigen/ major histocompatibility complex. J Exp Med 160:947–952PubMedCrossRefGoogle Scholar
  61. 61.
    Ryder LP, Svejgaard A, Dausset J (1981) Genetics of HLA disease association. Ann Rev Genet 15:169–187PubMedCrossRefGoogle Scholar
  62. 62.
    Saha BK, Cullen SE (1985) Molecular analysis of two mouse I-region recombinants. In: Streilein et al. (eds) Advances in gene technology: molecular biology of the immune system. Cambridge University Press, Cambridge, p 281–282Google Scholar
  63. 63.
    Saito H, Maki RA, Clayton LK, Tonegawa S (1983) Complete primary structures of the Eβ chain and gene of the mouse major histocompatibility complex. Proc Natl Acad Sci USA 80:5520–5524PubMedCrossRefGoogle Scholar
  64. 64.
    Shiroishi T, Sagai T, Moriwaki K (1982) A new wild-derived H-2 haplotype enhancing K-IA recombination. Nature 300:370–372PubMedCrossRefGoogle Scholar
  65. 65.
    Steinmetz M, Hood L (1983) Genes of the major histocompatibility complex in mouse and man. Science 222:727–733PubMedCrossRefGoogle Scholar
  66. 66.
    Steinmetz M, Minard K, Horvath S, McNicholas J, Frelinger J, Wake C, Long E, Mach B, Hood L (1982) A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature 300:35–42PubMedCrossRefGoogle Scholar
  67. 67.
    Steinmetz M, Malissen M, Hood L, Örn A, Maki RA, Dastornikoo GR, Stephan D, Gibb E, Romaniuk R (1984) Tracts of high or low sequence divergence in the mouse major histocompatibility complex. EMBO J 3:2995–3003PubMedGoogle Scholar
  68. 68.
    Taniguchi M, Tokukisa T, Hoh T, Kanno M (1984) Functional roles of two polypeptide chains that compose an antigen-specific suppressor T cell factor. J Exp Med 159:1096–1104PubMedCrossRefGoogle Scholar
  69. 69.
    Toyonaga B, Yanagi Y, Suciu-Foca N, Minden M, Mak TW (1984) Rearrangements of T-cell receptor gene YT35 in human DNA from thymic leukemia T-cell lines and functional T-cell clones. Nature 311:385–387PubMedCrossRefGoogle Scholar
  70. 70.
    Unanue ER, Beller DI, Lu CY, Allen PM (1984) Antigen presentation: comments on its regulation and mechanism. J Immunol 132:1–5PubMedGoogle Scholar
  71. 71.
    Wake CT, Widera G, Flavell RA (1985) Organization and expression of the murine MHC. In: Streilein et al. (eds) Advances in gene technology: molecular biology of the immune system. Cambridge University Press, Cambridge, p 33–36Google Scholar
  72. 72.
    Webb DR, Kapp JA, Pierce CW (1983) The biochemistry of antigen-specific T-cell factors. Ann Rev Immunol 1:423–438CrossRefGoogle Scholar
  73. 73.
    Weiss EH, Golden L, Fahrner K, Mellor AL, Devlin JJ, Bullman H, Tiddens H, Bud H, Flavell RA (1984) Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse. Nature 310:650–655PubMedCrossRefGoogle Scholar
  74. 74.
    White PC, New MI, Dupont B (1984) HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydrox-ylation. Proc Natl Acad Sci USA 81:7505–7509PubMedCrossRefGoogle Scholar
  75. 75.
    Widera G, Flavell RA (1984) The nucleotide sequence of the murine I-Eβ b immune response gene: evidence for gene conversion events in class II genes of the major histocompatibility complex. EMBO J 3:1221–1225PubMedGoogle Scholar
  76. 76.
    Widera G, Flavell RA (1985) The I-region of the C57BL/10 mouse: characterization and physical linkage to H-2 K of a novel, SBbeta-like class II pseudogene, Abeta3. Proc Natl Acad Sci USA 82:5500–5504PubMedCrossRefGoogle Scholar
  77. 77.
    Winoto A, Steinmetz M, Hood L (1983) Genetic mapping in the major histocompatibility complex by restriction enzyme site polymorphisms: most mouse class I genes map to the Tla complex. Proc Natl Acad Sci USA 80:3425–3429PubMedCrossRefGoogle Scholar
  78. 78.
    Wu TT, Kabat EA (1970) An analysis of sequences of variable regions of Bence-Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med 132:211–250PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • M. Steinmetz

There are no affiliations available

Personalised recommendations