New Thoughts on the Control of Self-Recognition, Cell Interactions, and Immune Responsiveness by Major Histocompatibility Complex Genes

  • David H. Katz


It is abundantly clear that our perceptions about the major histocompatibility complex (MHC) have changed quite substantially during the 1970’s. No longer does the term histocompatibility connote merely identities, similarities, or differences among tissue-transplantation antigens inherited by each individual member of a given species. Now, that term stands for a polymorphic family of genes and molecules the biological functions of which appear to play central roles in governing cell differentiation, cell-cell recognition, quality as well as quantity of immunological responsiveness, and probably a variety of other functions that have yet to be discovered. The realization that the biological importance of the MHC is broader than had initially been apparent has generated considerable excitement, a flurry of basic research endeavors, and an increasingly voluminous literature that becomes more and more difficult to keep track of and, at times, to understand. As can be expected, much of the literature, particularly recently, tends to be a bit repetitious in terms of both experimental approach and interpretation of data, a situation that seems to be inevitable whenever a given area of science is highly popular and pursued by large numbers of investigators. In view of this problem, this chapter was purposely prepared with its main goal being to share some new thinking, supported in part by new data, on some rather well-worn topics pertaining to involvement of MHC genes and molecules in immunological responses.


Helper Activity Adaptive Differentiation Bone Marrow Chimera Complex Antigenic Determinant Partner Cell 
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  1. Bach, F.H., Widmer, M.B., Bach, M.L., and Klein, J., 1972, Serologically defined and lymphocyte-defined components of the major histocompatibility complex in the mouse, J. Exp. Med. 136:1430.PubMedCrossRefGoogle Scholar
  2. Benacerraf, B., 1978, A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes, J. Immunol. 120:1809.PubMedGoogle Scholar
  3. Benacerraf, B., and McDevitt, H.O., 1972, Histocompatibility-linked immune response genes, Science 175:273.PubMedCrossRefGoogle Scholar
  4. Bevan, M.J., 1975, The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens, J. Exp. Med. 142:1349.PubMedCrossRefGoogle Scholar
  5. Bevan, M.J., 1977, In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells, Nature (London) 269:417.CrossRefGoogle Scholar
  6. Bevan, M.J., and Fink, P.J., 1978, The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells, Immunol. Rev. 42:3.PubMedCrossRefGoogle Scholar
  7. Binz, H., and Wigzell, H., 1977a, Antigen-binding, idiotypic T-lymphocyte receptors, in: Contemporary Topics in Immunobiology (O. Stutman, ed.), p. 113, Springer Science+Business Media New York.CrossRefGoogle Scholar
  8. Binz, H., and Wigzell, H., 1977b, Antigen-binding, idiotypic receptors from T lymphocytes: An analysis of their biochemistry, genetics, and use as immunogens to produce specific immune tolerance, in: Origins of Lymphocyte Diversity, Cold Spring Harbor Symp. Quant. Biol. 41:275.CrossRefGoogle Scholar
  9. Blanden, R.V., Doherty, P.C., Dunlop, M.B.C., Gardner, I.D., and Zinkernagel, R.M., 1975, Genes required for cytotoxicity against virus-infected target cells in K and D regions of H-2 complex, Nature (London) 254:269.CrossRefGoogle Scholar
  10. Dunham, E.K., Unanue, E.R., and Benacerraf, B., 1972, Antigen binding and capping by lymphocytes of genetic nonresponder mice, J. Exp. Med. 136:403.PubMedCrossRefGoogle Scholar
  11. Fink, P.J., and Bevan, M.J., 1978, H-2 antigens of the thymus determine lymphocyte specificity, J. Exp. Med. 148:766.PubMedCrossRefGoogle Scholar
  12. Gordon, R.D., Simpson, E., and Samelson, L.E., 1975, In vitro cell-mediated immune responses to the male specific (H-Y) antigen in mice, J. Exp. Med. 142:1108.PubMedCrossRefGoogle Scholar
  13. Hämmerling, G.J., Masuda, T., and McDevitt, H.O., 1973, Genetic control of the immune response: Frequency and characteristics of antigen-binding cells in high and low responder mice, J. Exp. Med. 137:1180.PubMedCrossRefGoogle Scholar
  14. Janeway, C.A., Jr., Wigzell, H., and Binz, H., 1976, Two different VH gene products make up the T-cell receptors, Scand. J. Immunol. 5:993.PubMedCrossRefGoogle Scholar
  15. Kappler, J.W., and Marrack, P., 1978, The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression, J. Exp. Med. 148:1510.PubMedCrossRefGoogle Scholar
  16. Katz, D.H., 1976, The role of the histocompatibility gene complex in lymphocyte differentiation, in Proceedings of the First International Symposium on the Immunobiology of Bone Marrow Transplantation, Transplant. Proc. 8:405.Google Scholar
  17. Katz, D.H., 1977a, The role of the histocompatibility gene complex in lymphocyte differentiation, in: Origins of Lymphocyte Diversity, Cold Spring Harbor Symp. Quant. Biol. 41:611.CrossRefGoogle Scholar
  18. Katz, D.H., 1977b, Lymphocyte Differentiation, Recognition, and Regulation, Academic Press, New York.Google Scholar
  19. Katz, D.H., 1980, Adaptive differentiation of lymphocytes: Theoretical implications for mechanisms of cell-cell recognition and regulation of immune responses, Adv. Immunol. 29:137.PubMedCrossRefGoogle Scholar
  20. Katz, D.H., and Benacerraf, B., 1975, Hypothesis: The function and interrelationships of T cell receptors, Ir genes and other histocompatibility gene products, Transplant. Rev. 22:175.PubMedGoogle Scholar
  21. Katz, D.H., and Benacerraf, B., 1976, Genetic control of lymphocyte interactions and differentiation, in The Role of Products of the Histocompatibility Gene Complex in Immune Responses (D.H. Katz and B. Benacerraf, eds.), p. 355, Academic Press, New York.Google Scholar
  22. Katz, D.H., Hamaoka, T., and Benacerraf, B., 1973a, Cell interactions between histoin-compatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral responses to hapten-protein conjugates, J. Exp. Med. 137:1405.PubMedCrossRefGoogle Scholar
  23. Katz, D.H., Hamaoka, T., Dorf, M.E., and Benacerraf, B., 1973b, Cell interactions between histoincompatible T and B lymphocytes. III. Demonstration that the H-2 gene complex determines successful physiologic lymphocyte interactions, Proc. Natl. Acad. Sci. U.S.A. 70:2624.PubMedCrossRefGoogle Scholar
  24. Katz, D.H., Hamaoka, T., Dorf, M.E., Maurer, P.H., and Benacerraf, B., 1973c, Cell interactions between histoincompatible T and B lymphocytes. IV. Involvement of the immune response (Ir) gene in the control of lymphocyte interactions in responses controlled by the gene, J. Exp. Med. 138:734.PubMedCrossRefGoogle Scholar
  25. Katz, D.H., Graves, M., Dorf, M.E., DiMuzio, H., and Benacerraf, B., 1975, Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex, J. Exp. Med. 141:263.PubMedCrossRefGoogle Scholar
  26. Katz, D.H., Chiorazzi, N., McDonald, J., and Katz, L.R., 1976, Cell interactions between histoincompatible T and B lymphocytes. IX. The failure of histoincompatible cells is not due to suppression and cannot be circumvented by carrier-priming T cells with allogeneic macrophages, J. Immunol. 117:1853.PubMedGoogle Scholar
  27. Katz, D.H., Skidmore, B.J., Katz, L.R., and Bogowitz, C.A., 1978, Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 → parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host, J. Exp. Med. 148:727.PubMedCrossRefGoogle Scholar
  28. Katz, D.H., Katz, L.R., Bogowitz, C.A., and Maurer, P.H., 1979, Adaptive differentiation of murine lymphocytes. II. (Responder × nonresponder) F1 cells can be taught to preferentially help nonresponder, rather than responder, B cells, J. Exp. Med. 150:20.PubMedCrossRefGoogle Scholar
  29. Kindred, B., and Shreffler, D.C., 1972, H-2 dependence of co-operation between T and B cells in vivo, J. Immunol. 109:940.PubMedGoogle Scholar
  30. Koszinowski, U., and Ertl, H., 1975, Lysis mediated by T cells and restricted by H-2 antigen of target cells infected with vaccinia virus, Nature (London) 255:552.CrossRefGoogle Scholar
  31. Krawinkel, U., Cramer, M., Berek, C., Hämmerling, G., Black, S.J., Rajewsky, K., and Eichmann, K., 1977, On the structure of the T-cell receptor for antigen, in: Origins of Lymphocyte Diversity, Cold Spring Harbor Symp. Quant. Biol. 41:285.CrossRefGoogle Scholar
  32. McDougal, J.S., and Cort, S.P., 1978, Generation of T helper cells in vitro. IV. F1 T helper cells primed with antigen-pulsed parental macrophages are genetically restricted in their antigen-specific helper activity, J. Immunol. 120:445.PubMedGoogle Scholar
  33. Miller, J.F.A.P., and Vadas, M.A., 1977, The major histocompatibility complex: Influence on immune reactivity and T-lymphocyte activation, Scand. J. Immunol. 6:771.PubMedCrossRefGoogle Scholar
  34. Ordal, J.C., and Grumet, F.C., 1972, Genetic control of the immune response: The effect of graft-versus-host reaction on the antibody responses to poly-L(Tyr,Glu)-poly-D,L-Ala—poly-L-Lys in nonresponder mice, J. Exp. Med. 136:1195.PubMedCrossRefGoogle Scholar
  35. Paul, W.E., Shevach, E.M., Thomas, D.W., Pickeral, S.F., and Rosenthal, A.S., 1977, Genetic restriction in T-lymphocyte activation by antigen-pulsed peritoneal exudate cells, in: Origins of Lymphocyte Diversity, Cold Spring Harbor Symp. Quant. Biol. 41:571.CrossRefGoogle Scholar
  36. Pierce, S.K., 1977, Recognition restrictions in lymphocyte collaborative interactions in IgG1 antibody responses, in: Immune System: Genetics and Regulation (E.E. Sercarz, L.A. Herzenberg, and C.F. Fox, eds.), p. 447, Academic Press, New York.Google Scholar
  37. Press, J.L., and McDevitt, H.O., 1977, Allotype-specific analysis of anti-(Tyr,Glu)-Ala-Lys antibodies produced by Ir-IA high and low responder chimeric mice, J. Exp. Med. 146:1815.PubMedCrossRefGoogle Scholar
  38. Rosenthal, A.S., 1978, Determinant selection and macrophage function in genetic control of the immune response, Immunol. Rev. 40:136.PubMedCrossRefGoogle Scholar
  39. Rosenthal, A.S., and Shevach, E.M., 1973, Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes, J. Exp. Med. 138:1194.PubMedCrossRefGoogle Scholar
  40. Schmitt-Verhulst, A.-M., and Shearer, G.M., 1975, Bifunctional major histocompatibility-linked genetic regulation of cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes, J. Exp. Med. 142:914.PubMedCrossRefGoogle Scholar
  41. Schwartz, R.H., 1978, A clonal deletion model for Ir gene control of the immune responses, Scand. J. Immunol. 7:3.PubMedCrossRefGoogle Scholar
  42. Shearer, G.M., 1974, Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes, Eur. J. Immunol. 4:527.PubMedCrossRefGoogle Scholar
  43. Skidmore, B.J., and Katz, D.H., 1977, Haplotype preference in lymphocyte differentiation. I. Development of haplotype-specific helper and suppressor activities in F1 hybrid activated T cell populations, J. Immunol. 119:694.PubMedGoogle Scholar
  44. Sprent, J., 1978, Restricted helper function of F1 → parent bone marrow chimeras controlled by K-end of H-2 complex, J. Exp. Med. 147:1838.PubMedCrossRefGoogle Scholar
  45. Swierkosz, J.E., Rock, K., Marrack, P., and Kappler, J.W., 1978, The role of H-2-linked genes in helper T-cell function. II. Isolation on antigen-pulsed macrophages of two separate populations of F1 helper T cells each specific for antigen and one set of parental H-2 products, J. Exp. Med. 147:554.PubMedCrossRefGoogle Scholar
  46. Thomas, D.W., and Shevach, E.M., 1978, Nature of the antigenic complex recognized by T lymphocytes. V. Genetic predisposition of independent F1 T cell subpopulations responsive to antigen-pulsed parental macrophages, J. Immunol. 120:445.Google Scholar
  47. von Boehmer, H., Hudson, L., and Sprent, J., 1975, Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras, J. Exp. Med. 142:989.CrossRefGoogle Scholar
  48. Waldmann, H., Pope, H., Bettles, C., and Davies, A.J.S., 1979, The influence of thymus on the development of MHC restrictions exhibited by T-helper cells, Nature (London) 277:137.CrossRefGoogle Scholar
  49. Yamashita, U., and Shevach, E.M., 1978, The histocompatibility restrictions on macrophage T-helper cell interaction determine the histocompatibility restrictions on T-helper cell B-cell interactions, J. Exp. Med. 148:1171.PubMedCrossRefGoogle Scholar
  50. Zinkernagel, R.M., and Doherty, P.C., 1974a, Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic chorimeningitis within a syngeneic or semiallogeneic system, Nature (London) 248:701.CrossRefGoogle Scholar
  51. Zinkernagel, R.M., and Doherty, P.C., 1974b, Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis, Nature (London) 251:547.CrossRefGoogle Scholar
  52. Zinkernagel, R.M., Callahan, G.N., Althage, A., Cooper, S., Klein, P.A., and Klein, J., 1978a, On the thymus in the differentiation of “H-2 self-recognition” by T cells: Evidence for dual recognition, J. Exp. Med. 147:882.PubMedCrossRefGoogle Scholar
  53. Zinkernagel, R.M., Callahan, G.N., Althage, A., Cooper, S., Streilein, J.W., and Klein, J., 1978b, The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: Evidence for T help, J. Exp. Med. 147:897.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1981

Authors and Affiliations

  • David H. Katz
    • 1
  1. 1.Department of Cellular and Developmental ImmunologyScripps Clinic and Research FoundationLa JollaUSA

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