Multiple Mechanisms of T Cell Tolerance to Mls-la

  • Marcia A. Blackman
  • John W. Kappler
  • Philippa Marrack
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 292)


A fundamental role of the immune system is to identify and destroy foreign antigens (Ag). A critical requirement of this function is the ability to distinguish between what is foreign, and should be eliminated, and what is “self” and should be tolerated. This lack of response to self is termed self-tolerance. Three mechanisms have been proposed for maintaining self tolerance-clonal deletion, or elimination of self-reactive clones, clonal anergy, or functional inactivation of self-reactive clones, and suppression, or negative regulation of self-reactive clones.


Transgenic Mouse Major Histocompatibility Complex Major Histocompatibility Complex Class Major Histocompatibility Complex Molecule Cell Tolerance 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Reviewed in P. Marrack and J. Kappler, The T cell receptor, Science 238:1073 (1987).CrossRefGoogle Scholar
  2. 2.
    P. J. Bjorkman, M. A. Saper, B. Samraoui, W. S. Bennett, J. L. Strominger, and D. C, Wiley, Structure of the human class 1 histocompatibility antigen, HLA-A2, Nature 329:506 (1987).PubMedCrossRefGoogle Scholar
  3. 3.
    P. J, Bjorkman, M. A. Saper, B. Samraoui, W. S. Bennett, J. L. Strominger, and D. C. Wiley, The foreign antigen binding site and T cell recognition regions of class I histocompatibility molecules, Nature 329:512 (1988).CrossRefGoogle Scholar
  4. 4.
    J. H. Brown, T. Jardetzky, M, A. Saper, B. Samraoui, P. J. Bjorkman, and D. C. Wiley, A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules, Nature 332:845 (1988).PubMedCrossRefGoogle Scholar
  5. 5.
    Reviewed in A. Weiss, J. Imboden, K. Hardy, B. Manger, C. Terhorst, and J. Stobo, The role of the T3/antigen receptor complex in T-cell activation, Ann. Rev. Immunol. 4:593 (1986).CrossRefGoogle Scholar
  6. 6.
    Reviewed in C. A. Janeway, Jr., T cell development: accessories or coreceptors, Nature 335:208 (1988).PubMedCrossRefGoogle Scholar
  7. 7.
    E, A. Clark and J. A. Ledbetter, Leukocyte cell surface enzymology:CD45(LCA, T200) is a protein tyrosine phosphatase, Immunol. Today 10:255 (1989).CrossRefGoogle Scholar
  8. 8.
    J. W. Kappler, U. Staerz, J. White, P. C. Marrack, Self-tolerance eliminates T cells specific for Mis-modified products of the major histocompatibility complex, Nature 332:35 (1988).PubMedCrossRefGoogle Scholar
  9. 9.
    Reviewed in P. Marrack and J. W. Kappler, The staphylococcal enterotoxins and their relatives, Science’, in press (1990).Google Scholar
  10. 10.
    J. Kappler, N. Roehm, P. Marrack, T cell tolerance by clonal elimination in the thymus, Cell 49:273 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    , A. M. Pullen, P. Marrack, J. W. Kappler, The T-cell repertoire is heavily influenced by tolerance to polymorphic self antigens, Nature 335:796 (1988).PubMedCrossRefGoogle Scholar
  12. 12.
    , H. R. Mac-Donald, R. Schneider, R. K. Lees, R. C. Howe, H. Acha Orbea, H. Festenstein, R. M. Zinkernagel, and H. Hengartner, T-cell receptor V use predicts reactivity and tolerance to Mlsa-encoded antigens, Nature 332:40 (1988).CrossRefGoogle Scholar
  13. 13.
    J. Bill, O. Kanagawa, D. Woodland, and E. Palmer, The MHC molecule I-E is necessary but not sufficient for clonal deletion of V11 -bearing T cells, J. Exp. Med. 169: 1405 (1989).PubMedCrossRefGoogle Scholar
  14. 14.
    , P. Kislelow, H. Bluthmann, U. D. Staerz, M. Steinmetz, and H. von Boehmer, Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes, Nature 333:742 (1988).CrossRefGoogle Scholar
  15. 15.
    , W. Sha, F. Nelson, R. Newberry, D. Kranz, J. Russell, and D. Loh, Positive and negative selection of an antigen receptor on T cells in transgenic mice, Nature 336:73 (1988).PubMedCrossRefGoogle Scholar
  16. 16.
    , L. Berg, B. Fazekas de St’Groth, A. Pullen, and M. Davis, Phenotypic differences between versus T-cell receptor transgenic mice undergoing negative selection, Nature 340:559 (1989).PubMedCrossRefGoogle Scholar
  17. 17.
    , M. P. Happ, D. L. Woodland, and E. Palmer, A third T-cell receptor -chain variable region gene encodes reactivity to Mls-la gene products, Proc. Natl. Acad. Sci. USA 86:6293 (1989).PubMedCrossRefGoogle Scholar
  18. 18.
    , H. Pircher, T. W. Mak, R. Lang, W. Ballhausen, E. Ruedi, H. Hengartner, R. M. Zinkernagel, and K. Burki, T cell tolerance to Mlsa-encoded antigens in T cell receptor V8.1 chain transgenic mice, EMBO J. 8:719 (1989).PubMedGoogle Scholar
  19. 19.
    , B. J. Fowlkes, R. H. Schwartz, and D. M. Pardoll, Deletion of self-reactive thymocytes occurs at a CD4+CD8+ precursor stage, Nature 334:620 (1988).PubMedCrossRefGoogle Scholar
  20. 20.
    , M. McDuffie, N. Roehm, J. Kappler, and P. C. Marrack, Involvement of major histocompatibility products in tolerance induction in the thymus, J. Immunol. 141:1840 (1988).Google Scholar
  21. 21.
    H. R. Mac-Donald, H. Hengartner, and T. Pedrazzini, Intrathymic deletion of self-reactive cells prevented by neonatal anti-CD4 antibody treatment, Nature 335:174 (1988).CrossRefGoogle Scholar
  22. 22.
    T. Finkel, J. Cambier, R. Kubo, W. Born, P. Marrack, and J. Kappler, The thymus has two functionally distinct populations of + T cells: one population is deleted by ligation of TCR, Cell 58:1047 (1989).PubMedCrossRefGoogle Scholar
  23. 23.
    H. R. Mac-Donald, T. Pedrazzini, R. Schneider, J. A. Louis, R. M. Zinkernagel, and H. Hengartner, Intrathymic elimination of Mlsa-reactive (V6) cells during neonatal tolerance induction of Mlsa-encoded antigens, J. Exp. Med. 167:2005 (1988).CrossRefGoogle Scholar
  24. 24.
    M. A. Blackman, J. Yague, R. Kubo, D. Gay, C. Coleclough, E. Palmer, J. Kappler, and P. Marrack, The T cell repertoire may be biased in favor of MHC recognition, Cell 47:349 (1986).PubMedCrossRefGoogle Scholar
  25. 25.
    M. Blackman and H. G.-Burgert, unpublished observations.Google Scholar
  26. 26.
    M. A. Blackman, H. G.-Burgert, D. L. Woodland, E. Palmer, J. W. Kappler, and P. Marrack, A role for clonal inactivation in T cell tolerance to Mls-la Nature (1990, in press).Google Scholar
  27. 27.
    M. A. Blackman, unpublished observations.Google Scholar
  28. 28.
    H.-G. Rammensee, R. Kroschewski, B. Frangoulis, Clonal anergy induced in mature V+ T lymphocytes on immunizing Mls-lb mice with Mls-la-expressing cells, Nature 339:541 (1989).PubMedCrossRefGoogle Scholar
  29. 29.
    L. C. Burkly, D. Lo, O. Kanagawa, R. L. Brinster, and R. A. Flavell, T cell tolerance by clonal anergy in transgenic mice with non-lymphoid expression of MHC class II IE, Nature 342:564 (1989).PubMedCrossRefGoogle Scholar
  30. 30.
    F. Ramsdell, T. Lantz, B. J. Fowlkes, A nondeletional mechanism of thymic self tolerance, Science 246:1038 (1989).PubMedCrossRefGoogle Scholar
  31. 31.
    M. Blackman and D. L. Woodland, unpublished observations.Google Scholar
  32. 32.
    K. Haskins, C. Hannum, J. White, N. Roehm, R. Kubo, J. Kappler, and P. Marrack, The major histocompatibility complex-restricted antigen receptor on T cells. VI. An antibody to a receptor allotype, J. Exp. Med. 160:452 (1984).PubMedCrossRefGoogle Scholar
  33. 33.
    U. D. Staerz, H.-G. Rammensee, J. D. Benedetto, M. J. Bevan, Characterization of amurine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor, J. Immunol. 134:3394 (1985).Google Scholar
  34. 34.
    O. Leo, M. Foo, D. H. Sachs, L. E. Samelson, and J. A. Bluestone, Identification of monoclonal antibody specific for a murine T3 polypeptide, Proc. Nat. Acad. Sci. USA 83:767 (1987).Google Scholar
  35. 35.
    J. Kappler, B. Skidmore, J. White, and P. Marrack, Antigen-inducible, H-2-restricted, interleukin 2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition, J. Exp. Med. 153:119 (1981).CrossRefGoogle Scholar
  36. 36.
    T. Mosmann, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J. Immunol. Methods 65:55 (1983).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Marcia A. Blackman
    • 1
    • 2
  • John W. Kappler
    • 1
    • 2
    • 4
  • Philippa Marrack
    • 1
    • 2
    • 3
    • 4
  1. 1.Howard Hughes Medical Institute at DenverNational Jewish Center for Immunology and Respiratory MedicineDenverUSA
  2. 2.Division of Basic Immunology, Department of MedicineNational Jewish Center for Immunology and Respiratory MedicineDenverUSA
  3. 3.Department of Biochemistry, Biophysics and GeneticsUniversity of Colorado Health Sciences CenterDenverUSA
  4. 4.Department of Microbiology, Immunology and MedicineUniversity of Colorado Health Sciences CenterDenverUSA

Personalised recommendations