H-2 Antigens pp 315-320 | Cite as

Mutation in the Aβ Gene of B6.C-H-2bm12. Antibody Binding Site VS. T Cell Recognition Sites

  • Kathleen A. Donovan
  • Sujay K. Singh
  • Chella S. David
Part of the NATO ASI Series book series (NSSA, volume 144)

Abstract

Four functional Ia genes are coded within the I (immune response) region of mouse, e.g., Aα, Aβ, Eα, and Eβ (Jones et al. 1978; Klein et al. 1981). In recent years using congenic inbred and recombinant strains of mice, several investigators have demonstrated a relationship between Ia molecules and immune response. The I-A mutant mouse strain, B6.C-H-2bm12 is to date the only known example of a mutant involving the class II genes. This strain was originally identified by Melvold and Kohn from a (B6 × BALB/c)F1 by reciprocal skin graft rejection. The findings on this mutant, B6.H-2bm12, have helped in further characterization of fine specificities on an Ia molecule. In analyzing this mutant strain, McKenzie and co-workers were able to map the mutation to the I-A subregion using complementation studies with recombinant strains. Tryptic peptide maps revealed a limited number of differences between 86 and bm12, mapping the mutation to the I-A beta polypeptide chain (McKean et al. 1981). The tryptic peptide studies showed that this mutation is not due to a single point mutation, but involves a minimum of three different amino acid substitutions. Recently, McIntyre and Seidman (1984) have cloned and sequenced a gene coding for the bm12 A-beta polypeptide chain. Three nucleotide substitutions result in three amino acid substitutions within a span of five amino acids; isoleucine at position 67, arginine at position 70 and threonine at position 71, are being substituted by phenylalanine, glutamine and lysine respectively (Fig. 1). Two of these amino acid substitutions (arginine-glutamine and threonine-lysine) are non-conservative changes in the tertiary structure of the beta polypeptide chain, resulting in the observed alterations in the serology and function of the bm12 I-A molecule. Amino acid sequence comparison also shows that two of the amino acid substitutions found in the bm12 A8 chain are found at the same positions in several human class II beta chains (McIntyre and Seidman, 1984). These comparisons suggest that the bm12 mutation in the I-A beta gene arose from a gene-conversion type event in which another class II beta chain gene acted as a donor sequence.

Keywords

Amino Acid Substitution Linear Determinant Gene Conversion Event Functional Determinant Antibody Binding Site 
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.

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References

  1. David, C.S., McCormick, J.F., Lafuse, W.P. and Hirose, S.: Serological confirmation in I-A mutant 86.C-H-2bm12 of gene conversion. Transplantation 42: 429–433, 1986.PubMedCrossRefGoogle Scholar
  2. Hansen, T.H. Walsh, W.D., Rubocki, R.J. and Kapp, J.A.: Responses of B6.C-H-2bm12 to heterologous insulins show no correlation with the putative gene conversion but define Iabm12 as functionally unique. J. Mol. Cell. Immunology 2: 359–368, 1986.Google Scholar
  3. Hochman, P.S., and Huber, B.T.: A class II gene-conversion event defines an antigen-specific Ir gene epitope. J. Exp. Med. 160: 1925–1930, 1984.PubMedCrossRefGoogle Scholar
  4. Huber, B.T., Hansen, T.H., Skelly, R.R. and Thorley-Lawson, D.A.: Ia.W39 expression correlated with a specific Ir Function. J. Immunology 128: 2349–2352, 1982.Google Scholar
  5. Johnson, E.D., Krco, C.J. and David, C.S.: la antigens are the stimulating determinants in the syngeneic mixed lymphocyte reaction. Transplantation 33: 552–555, 1982.PubMedCrossRefGoogle Scholar
  6. Jones, P.P., Murphy, D.B. and McDevitt, H.O.: Two-gene control of the expression of murine la antigens. J. Exp. Med. 148: 925–939, 1978.PubMedCrossRefGoogle Scholar
  7. Klein, J., Juretic, A., Baxevanis, C.N. and Nagy, Z.A.: The traditional and a new version of the mouse H-2 complex. Nature (Lond.) 291: 455–460, 1981.CrossRefGoogle Scholar
  8. Lafuse, W.P., McCormick, J.F., Melvold, R.N. and David, C.S.: Serological and biochemical analysis of la molecules in the I-A mutant B6.C-H-26m12. Transplantation 31: 434–438, 1981.PubMedCrossRefGoogle Scholar
  9. Lin, C.S., Rosenthal, A.S., Passmore, H.C. and Hansen, T.H.: Selective loss of antigen-specific Ir gene function in Ia mutant B6.C-H-2bm12 is an antigen-presenting cell defect. Proc. Natl. Acad. Sci. USA 78: 6406–6410, 1981.PubMedCrossRefGoogle Scholar
  10. McIntyre, K.R. and Seidman, J.G.: Nucleotide sequence of the mutant I-Abm12 genes is evidence for genetic exchange between mouse immune response genes. Nature 308: 551–553, 1984.PubMedCrossRefGoogle Scholar
  11. McKean, D.J., Melvold, R.W. and David, C.S.: Tryptic peptide comparison of la antigen and polypeptides from the I-A mutant B6.C-H-2bm12 and its congenic parental strain 86. Immunogenetics 14: 41–51, 1981.PubMedCrossRefGoogle Scholar
  12. McKenzie, I.F.C., Morgan, G.M., Sandrin, M.S., Michaelides, M.M., Melvold, R.W. and Kohn, H.I.: B6.C-H-2bm12 a new H-2 mutation in the I region in the mouse. J. Exp. Med. 150: 1323–1338, 1979.PubMedCrossRefGoogle Scholar
  13. Melvold, R.N. and Kohn, H.I.: Eight new histocompatibility mutations associated with the H-2 complex. Immunogenetics 3: 185–191, 1976.CrossRefGoogle Scholar
  14. Mengle-Gaw, L., Conner, S., McDevitt, H.O. and Fathman, C.G.: Gene conversion between murine class II major-histocompatibility complex loci. Functional and molecular evidence from the bm12 mutant. J. Exp. Med. 160: 1184–1194, 1984.PubMedCrossRefGoogle Scholar
  15. Steinmuller, D.: Skin grafting. Methods in Immunology 108: 20–28, 1984.Google Scholar
  16. Tse, H.Y., Kanamori, S., Walsh, W.D. and Hansen, T.H.: The murine bm12 gene conversion provides evidence that T cells recognize predominantly Ia conformation. Proc. Natl. Acad. Sci. USA 82: 7058–7062, 1985.PubMedCrossRefGoogle Scholar
  17. Widera, G. and Flavell, R.A.: The nucleotide sequence of the murine I-E immune response gene: Evidence for gene conversion events in class II genes of the major histocompatibility complex. EMBO Journal 3: 1221–1225, 1984.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Kathleen A. Donovan
    • 1
  • Sujay K. Singh
    • 1
  • Chella S. David
    • 1
  1. 1.Department of ImmunologyMayo Clinic and Medical SchoolRochesterUSA

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