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Self la-recognizing T cells undergo an ordered series of interactions with ia-bearing substrate cells of defined function during their development: A model

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Conclusion

A four-step scheme of cell interactions between self la-recognizing T cells in the helper T cell lineage and la-bearing substrate cells is proposed. The first interaction, with a veto cell, clears the repertoire of helper T cells specific for self Ia, or self antigens in association with self Ia. The second interaction, between helper T cells and Ia on thymic epithelium expands self Ia-recognizing T cells; T cell diotopes displayed on the epithelial cell surface may play the role of an internal antigenic image for this expansion. The third interaction occurs between antigen-presenting cell Ia plus nominal antigen and virgin Lyl T cells, leading to T cell activation and expansion. The fourth interaction involves B cells binding specific antigen via their Ig receptor and displaying self Ia, and this antigen-Ia complex is recognized by helper T cells, causing B cell proliferation and differentiation to antibody secretion. A regulatory pathway, involving suppressor T cells that recognize activated helper T cells via self Ia bound to the anti-self Ia receptor on the T cell surface, is also proposed. This model permits any or all of the proposed mechanisms of Ir gene ac tion, and is compatible with one or two site models of T cell receptors. Its main predictions are that Ia density is carefully regulated in substrate cells to allow both self tolerance and self recognition, in an ordered scheme of development.

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References

  1. Miller, R.G.: An immunological suppressor cell inactivating cytotoxic T lymphocyte precursor cells recognizing it. Nature, Lond.287: 544–546 (1980).

    Article  CAS  Google Scholar 

  2. Morrisey, P.J., Kruisbeck, A.M.; Sharrow, S.O.; Singer, A.: Tolerance of thymic cytotoxic T lymphocytes to allogeneic H-2 determinants encountered prethymically. Evidence for expression of anti-H-2 receptors prior to entry into the thymus. Proc. natn. Acad. Sci. USA79: 2003–2007 (1982).

    Article  Google Scholar 

  3. Doherty, P.C.: Surveillance of self. CMI to virally modified cell surface defined operationally by the MHC. Prog. Immunol.4: 563–576 (1980).

    Google Scholar 

  4. Rouse, R.V.; Ewijk, W. van; Jones, P.P.; Weissman, I.: Expression of MHC antigens by mouse thymic dendritic cells. J. Immun.122: 2508–2515 (1979).

    PubMed  CAS  Google Scholar 

  5. Jason, J.M.; Janeway, CA., Jr.: In vitro cultivation of non-lymphoid thymic cells. Morphological and immunological characterization (submitted for publication).

  6. Janeway, C.A., Jr.: The selection of self MHC recognizing T lymphocytes. A role for idiotypes? Immunol. Today3: 261–265 (1982).

    Article  Google Scholar 

  7. Nussenzweig, M.C.; Steinman, R.M.; Unkeless, J.C.; Witmer, M.I.; Gutchinor, B.; Cohn, Z.A.: Study of the cell surface of mouse dendritic cells and other leukocytes. J. exp. Med.154: 168–187 (1981).

    Article  PubMed  CAS  Google Scholar 

  8. Cowing, C.; Pincus, S.H.; Sachs, D.H.; Dickler, H.B.: A subpopulation of adherent accessory cells being both I-A and I-E or C subregion antigens is required for antigen-specific murine T lymphocyte proliferation. J. Immun.121: 1680–1686 (1978).

    PubMed  CAS  Google Scholar 

  9. Katz, M.: Jones, B.; Janeway, C.A., Jr.: Cloned T cell lines do not discriminate between self-Ia molecules on B cells and antigen presenting cells; in Pierce, Ir genes: past, present and future (Humana Press, Clifton, in press).

  10. Chesnut, R.W.; Grey, H.A.: Studies on the capacity of B cells to serve as antigen presenting cells. J. Immun.126: 1075–1079 (1981).

    PubMed  CAS  Google Scholar 

  11. McKean, DJ.; Infante, A.J.; Nilson, A.; Kimoto, M.; Fathmann, C.G.; Walker, E.; Warner, N.: Major histocompatibility complex restricted antigen presentation to antigen reactive T cells by B lymphocyte tumor cells. J. exp. Med.154: 1419–1431 (1981).

    Article  PubMed  CAS  Google Scholar 

  12. Chesnut, R.W.; Colon, S.M.; Grey, H.M.: Antigen presentation by normal B cells, B cell tumors, and splenic macrophages. Functional and biochemical comparison. J. Immun.128: 1764–1768 (1982).

    PubMed  CAS  Google Scholar 

  13. Britz, J.S.; Askenase, P.W.; Ptak, W.; Steinman, R.M.; Gershon, R.K.: Specialized antigen presenting cells. Splenic dendritic cells and peritoneal exudate cells induced by mycobacteria activate effector T cells that are resistant to suppression. J. exp. Med.155: 1344–1356(1982).

    Article  PubMed  CAS  Google Scholar 

  14. Ptak, W.; Rozycka, D.; Askenase, P.W.; Gershon, R.K.: Role of antigen presenting cells in the development and persistence of contact hypersensitivity. J. exp. Med.151: 362–375 (1980).

    Article  PubMed  CAS  Google Scholar 

  15. Britz, J.S.; Jason, J.M.; Ptak, W.; Janeway, C.A., Jr.; Gershon, R.K.: Distinctive immunological properties of cultured murine thymic epithelial cells (submitted for publication).

  16. Greene, M.I.; Sugimoto, M.; Benacerraf, B.: Mechanisms of regulation of cell-mediated immune responses. I. Effect of the route of immunization with TNP-coupled syngeneic cells on the induction and suppression of contact sensitivity to picryl chloride. J. Immun.120: 1604–1611 (1978).

    PubMed  CAS  Google Scholar 

  17. Cohen, B.E.; Paul, W.E.: Macrophage control of time-dependent changes in antigen sensitivity of immune T lymphocyte populations. J. Immun.112: 359–369(1974).

    PubMed  CAS  Google Scholar 

  18. Jones, B.; Janeway, CA., Jr.: Cooperative interaction of B lymphocytes with antigen-specific helper T lymphocytes is MHC restricted. Nature, Lond.292: 547–549 (1981).

    Article  CAS  Google Scholar 

  19. Katz, D.H.: Adoptive differentiation of murine lymphocytes. III. T and B lymphocytes display reciprocal preference for one another to develop optimal interacting partner cell sets. J. Immun.122: 1937–1942 (1979).

    PubMed  CAS  Google Scholar 

  20. Conrad, P.J.; Lerner, E.A.; Jones, P.P.; Murphy, D.B.; Janeway, C.A., Jr.: Selected expression of Ia glycoprotein antigens in Fl hybrid mice detected with alloreactive cloned T cell lines. J. Immun.129: 2616–2620 (1982).

    PubMed  CAS  Google Scholar 

  21. Katz, D.H.; Skidmore, B.J.; Katz, L.R.; Bogowitz, C.A.: Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in Fl → parental chimeras manifest preferential cooperation activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host. J. exp. Med.148: 727–745 (1978).

    Article  PubMed  CAS  Google Scholar 

  22. Henry, C.; Chen, E.L.; Kochlin, D.: Expression and function of I region products on immunological cells. II. I region products T-B interactions. J. Immun.119: 744–752 (1977).

    PubMed  CAS  Google Scholar 

  23. Cantor, H.; Gershon, R.K.: Immunological circuits. Cellular composition. Fed. Proc.38: 2058–2064(1979).

    PubMed  CAS  Google Scholar 

  24. Bellgrau, D.; Wilson, D.B.: Immunological studies of T cell receptors. I. Specifically induced resistance to graft-versus-host disease in rats mediated by host T cell immunity to alloreactive parental T cells. J. exp. Med.148: 103–113 (1978).

    Article  PubMed  CAS  Google Scholar 

  25. Bellgrau, D.; Wilson, D.B.: Immunological studies of T cell receptors. II. Limited polymorphorism of idiotype determinants on T cell receptors specific for major histocompatibility alloantigens. J. exp. Med.149:234–243 (1979).

    Article  PubMed  CAS  Google Scholar 

  26. Woodland, R.I.; Wilson, D.B.: The induction of specific resistance in Fl hybrid rats to local graft-vs-host reactions. Nature of the eliciting cells. Eur. J. Immunol.7: 136–142(1977).

    Article  PubMed  CAS  Google Scholar 

  27. Katz, D.H.; Katz, L.R.; Bogowitz, C.A.: Cell interaction molecules on immunocompetent lymphocytes. Development of anti-parent cell interaction molecule receptor reactions in Fl mice and evidence for a unique Fl hybrid subset of interacting cells. J. exp. Med.153: 407–422 (1981).

    Article  PubMed  CAS  Google Scholar 

  28. Germain, R.N.; Benacerraf, B.: Helper and suppressor T cell factors. Springer Semin. Immunopath.3: 93–147 (1980).

    CAS  Google Scholar 

  29. Tada, T.; Okumura, K.: The role of antigen-specific T cell factors in the immune response. Adv. Immunol.28: 1–87 (1979).

    Article  PubMed  CAS  Google Scholar 

  30. Jerne, N.K.: Towards a network theory of the immune system. Ann. Immunol., Paris1250: 373- 389(1974).

    Google Scholar 

  31. Janeway, CA., Jr.; Wigzell, H.; Binz, H.: Hypothesis. Two different VH gene products make up the T cell receptor. Scand. J. Immunol.5: 993- 1001 (1976).

    Article  PubMed  CAS  Google Scholar 

  32. McNicholas, J.M.; Murphy, D.B.; Matis, L.A.; Schwartz, R.H.; Lerner, E.A.; Janeway, C.A., Jr.; Jones, P.P.: Immune response gene function correlates with the expression of an Ia antigen. I. Preferential association of certain Ae and Eα chains results in a quantitative deficiency in expression of an Ae:Eα complex. J. exp. Med.155: 490–507 (1982).

    Article  PubMed  CAS  Google Scholar 

  33. Matis, L.A.; Jones, P.P.; Murphy, D.B.; Hedrick, S.M.; Lerner, E.A.; Janeway, CA., Jr.; McNicholas, J.M.; Schwartz, R.H.: Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in Ae:Eα complex expression causes a corresponding defect in antigen-presenting cell function. J. exp. Med.155:508–522(1982).

    Article  PubMed  CAS  Google Scholar 

  34. Nakano, K.; Nakamura, I.; Cudkowicz, G.: Generation of Fl hybrid cytotoxic T lymphocytes specific for self H-2. Nature, Lond.282: 559–563 (1981).

    Article  Google Scholar 

  35. Nakano, K.; Nakamura, I.; Cudkowicz, G.: Fl hybrid anti-parental H-2b cell mediated lympholysis: genetic control of target antigens by the H-2D region. J. Immun.127: 173–178 (1981).

    PubMed  CAS  Google Scholar 

  36. Janeway, C.A., Jr.: The specificity of T lymphocyte responses to chemically defined antigens. Transplant. Rev.29: 164–188 (1976).

    PubMed  CAS  Google Scholar 

  37. Schwartz, R.H.: Functional properties of I region gene products and theories of immune response (Ir) gene function; in Ferrone, David, Ia antigens and their analogues in man and other animals (CRC Press, Boca Raton, in press).

  38. Ishii, N.; Nagi, Z.; Klein, J.: Restriction molecules involved in the interaction of T cells with allogeneic antigen presenting cells. J. exp. Med.156: 622–627(1982).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Howard Hughes Medical Institute at Yale, Department of Pathology, Yale Medical School, 06511, New Haven, Conn., USA

    Charles A. Janeway & Michael E. Katz

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  1. Charles A. Janeway
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  2. Michael E. Katz
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Supported by NIH grant AI-14579 and the Howard Hughes Medical Institute.

Investigator, Howard Hughes Medical Institute.

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Janeway, C.A., Katz, M.E. Self la-recognizing T cells undergo an ordered series of interactions with ia-bearing substrate cells of defined function during their development: A model. Surv. immunol. Res. 3, 45–54 (1984). https://doi.org/10.1007/BF02918597

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