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Genetic Control of the Immune Response to Hemoglobin and its Subunits

  • Christopher J. Krco
  • A. Latif Kazim
  • M. Zouhair Atassi
  • Chella S. David
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 150)

Summary

Human adult hemoglobin (Hb) was selected as a model oligomeric protein for investigations into Ir gene function. Separate genetic control of the α- and β-subunits of Hb was demonstrated. The relevant Ir genes were mapped to the I-A subregion and in particular to the Aβ gene for the α-chain of Hb. H-2b and H-2d mice are responders to the α-subunit and H-2d, H-2f and H-2s mice are responsive to the β-subunit. The subunits are not cross-reactive in T-cell assays. Non-H-2 linked genes are also important in Hb-specific immunity. There is a requirement for Ly-1+ T-cells for optimal responses in vitro.

Keywords

Genetic Control Antigenic Site High Responder Sperm Whale Myoglobin Separate Genetic Control 
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. 1.
    C.J. Krco and C.S. David. Genetics of immune responses: A survey. CRC Critical Rev. Immunol. 1, 211 (1981).Google Scholar
  2. 2.
    E.C. Lozner, D.H. Sachs, and G.M. Shearer. Genetic control of the immune response to staphylococcal nuclease. I. Ir-nase control of the antibody response to nuclease by the Ir region of the mouse H-2 complex. J. Exp. Med. 139, 1204 (1974).PubMedCrossRefGoogle Scholar
  3. 3.
    K. Okuda, P. Christadoss, S. Twining, M.Z. Atassi, and C.S. David. Genetic control of immune response to sperm whale myoglobin in mice. I. T-lymphocyte proliferative response under H-2 linked Ir gene control. J. Immunol. 121, 866 (1978).PubMedGoogle Scholar
  4. 4.
    K. Okuda, S.S. Twining, C.S. David, and M.Z. Atassi. Genetic control of immune response to sperm whale myoglobin in mice. II. T-lymphocyte proliferative response to the synthetic antigenic sites. J. Immunol. 23, 182 (1979).Google Scholar
  5. 5.
    M.Z. Berzofsky. Genetic control of the immune response to mammalian myoglobins in mice. I. More than one I-region in H-2 controls the antibody response. J. Immunol. 120, 260 (1978)Google Scholar
  6. 6.
    S. Yokota, C.S. David and M.Z. Atassi. Genetic control of the immune response to myoglobin. III. Autoimmune T-lympho- cyte proliferative response to mouse myoglobin. Mol. Immunol. 17, 1079 (1980).PubMedCrossRefGoogle Scholar
  7. 7.
    S.S. Twining, C.S. David and M,Z. Atassi. Genetic control of the immune response to myoglobin. IV. Mouse antibodies in out bred and congenic strains against sperm-whale myoglobin recognize the same antigenic sites that are recognized by antibodies raised in other species. Mol. Immunol, 18, 447 (1981).PubMedCrossRefGoogle Scholar
  8. 8.
    M.Z. Atassi, S.S. Twining, H. Lehmann and C.S, David. Genetic control of the immune response to myoglobin. V, Analysis of the cross-reactivity of 12 myoglobins with sperm-whale myoglobin antisera of inbred mouse strains in terms of substitutions in the antigenic sites and in the environmental residues of the sites. Immunol. Commun. 10, 359 (1981).PubMedGoogle Scholar
  9. 9.
    M.Z. Atassi, S. Yokota, S.S. Twining, H. Lehman and C,S. David Genetic control of the immune response to myoglobin. VI. Inter-site influences in T-lymphocyte proliferative response from analysis of cross-reactions of ten myoglobins in terms of substitutions in the antigenic sites and in environmental residues of the sites. Mol. Immunol. 18, 945 (1981).PubMedCrossRefGoogle Scholar
  10. 10.
    R.H. Schwartz, A.M. Solinger, M, Utlee and E. Margoliash. In Immunobiology of Proteins and Peptides (edited by M.Z. Atassi and A.B. Stavitsky ) p. 371, Plenum Press, New York (1978).Google Scholar
  11. 11.
    E.E. Sercarz, R.L. Yowel, D. Turkin, A. Miller, B.A. Araneo and L. Adorini. Different functional specificity repertories for suppressor and helper T-cells. Immunological Rev. 39, 108 (1978).CrossRefGoogle Scholar
  12. 12.
    K. Okuda, S. Sakata, M.Z. Atassi and C,S. David. Genetic control of the immune response to hen’s egg-white lysozyme in mice. I. Antibody and T-lymphocyte proliferative responses to the native protein. J. Immunogen. 6, 447 (1979).CrossRefGoogle Scholar
  13. 13.
    I. Melchers, and K. Rajewsky. Specific control of responsive- ness by two complementing Ir loci in the H-2 complex. Eur. J. Immunol. 5, 753 (1975).Google Scholar
  14. 14.
    I. Melchers, K. Rajewsky and D.C. Shreffler. Ir-LDHg: map position and functional analysis. Eur. J. Immunol, 5,754. (1973).CrossRefGoogle Scholar
  15. 15.
    L.J. Rosenwasser, M.Z. Barcinski, R.H. Schwartz, and A.S, Rosenthal. Immune response gene control of determinant selection. II. Genetic control of the murine T lymphocyte proliferative response to insulin. J. Immunol. 123, 471 (1979).PubMedGoogle Scholar
  16. 16.
    P. Christadoss, Y-C.M. Kong, M. Elrehewy, N.R. Rose and C.S. David. Genetic control of T-lymphocyte proliferative autoimmune response to thyroglobulin in mice. In: Genetic Con- trol of Autoimmune Disease (edited by Rose, Bigazzi and Warner ) p. 445, Elsevier-North Holland. (1978).Google Scholar
  17. 17.
    Y-C.M. Kong, C.S. David, A.A. Giraldo, M. Elrehewy and N.R. Rose. Regulation of autoimmune response to mouse thyroglobulin: influence of H-2D-end genes. J. Immunol. 123, 5 (1979).Google Scholar
  18. 18.
    A.L. Kazim and M.Z. Atassi. Prediction and confirmation by synthesis of two antigenic sites in human hemoglobin by extrapolation from the known antigenic structure of sperm-whale myoglobin. Biochem. J. 167, 275 (1977).PubMedGoogle Scholar
  19. 19.
    A.L. Kazim and M.Z. Atassi. A novel and comprehensive synthetic approach for the elucidation of protein antigenic structures: Determination of the full antigenic profile of the a-chain of human hemoglobin. Biochem, J. 191, 261 (1980).Google Scholar
  20. 20.
    C.J. Krco, A.L. Kazim, M.Z. Atassi and C.S. David, Genetic control of the immune response to hemoglobin. I. Demonstration of separate genetic control of the responses to the a-and P.-subunits by in vitro lymphocyte proliferation. J. Immunogenet. 8, 315 (1981).Google Scholar
  21. 21.
    C.J. Krco, A.L. Kazim, M.Z. Atassi and C,S, David. Genetic control of the immune response to hemoglobin. II. Studies using purified a-chain and 8-chain as immunogens. J. Immunogenet. 8, 395 (1981).PubMedCrossRefGoogle Scholar
  22. 22.
    C.J. Krco, A.L. Kazim, M,Z. Atassi, R. Melvold and C.S. David Genetic control of the immune response to hemoglobin. III. Variant A8 (bm12) but not Ae (D2.GD) la polypeptides alter immune responsiveness towards the a-subunit of human hemoglobin. J. Immunogenet. (in press) (1981).Google Scholar
  23. 23.
    C.R. Young. Genetic control of the immune response to ferritin in mice. J. Immunogenet. 3, 199 (1976).PubMedCrossRefGoogle Scholar
  24. 24.
    C.R. Young. Genetic control of the immune response to mammalian chymotrypsins in mice. J. Immunogenet. 6, 45 (1979).PubMedCrossRefGoogle Scholar
  25. 25.
    N.M. Vaz, E.M. Vaz and B.B. Levin. Relationship between histocompatibility (H-2) and genotype and immune responsiveness to low doses of ovalbumin in the mouse. J. Immunol. 104, 1572 (1970).PubMedGoogle Scholar
  26. 26.
    J.A. Marsh, T.E. Wheat and E. Goldberg. Temporal regulation of the immune response to LDH-C4 by an X-linked gene in C3H/HeJ and SJL/J mice. J. Immunol. 118, 2293 (1977).PubMedGoogle Scholar
  27. 27.
    H. Nowack, E. Hahn, C.S, David, R. Timpl and D. Gotze. Immune response to calf collagen Type I in mice: a combined control of Ir-IA and non-H-2 linked genes. Immunogenet. 2, 331 (1975).CrossRefGoogle Scholar
  28. 28.
    D.H. Sachs, J.Z. Berzofsky, D.C. Pisetsky and R.H. Schwartz Genetic control of the immune response to staphylococcal nuclease. Springer Semin. Immunopath. 1, 51 (1978).CrossRefGoogle Scholar
  29. 29.
    C.J. Krco, A.L. Kazim, M.Z. Atassi and C.S. David. Genetic control of the immune response to hemoglobin. IV. Ly-l+ T-cells and appropriate non-H-2 genes are required for in vitro responses to a-and 8-subunits of human adult hemoglobin. J. Immunogenet. 8, 471 (1981).PubMedCrossRefGoogle Scholar
  30. 30.
    M.E. Dorf and B. Benacerraf. Complementation of H-2 linked Ir genes in the mouse. Proc. Natl. Acad. Sci. 72, 3671 (1975).CrossRefGoogle Scholar
  31. 31.
    W.P. Lafuse, J.F. McCormick, R.W, Melvold, and C.S, David, Serological and biochemical analysis of la molecules in the I-A mutant B6.C-H-21m12. Transpl. 31, 434 (1981).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Christopher J. Krco
    • 1
  • A. Latif Kazim
    • 1
  • M. Zouhair Atassi
    • 1
  • Chella S. David
    • 1
  1. 1.Department of ImmunologyMayo ClinicRochesterUSA

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