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KLH-specific, I-E/C-restricted clones of proliferating T lymphocytes

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Abstract

The recognition of keyhole limpet hemocyanin by a substantial proportion of proliferating clones of murine T lymphocytes was found to be restricted by the I-E/Ck molecule, which is a combinatorial product of genes located in the I-A (Ae) and I-EIC (Eα) subregions of the murine major histocompatibility complex. The respective roles of the Ae (polymorphic) and Eα (oligomorphic) gene products in the expression of the structures which are used as restriction elements by these T-cell clones was analyzed by mating parental strains unable to present the antigen and bearing selected Ae and Eα alleles. Efficient complementation for antigen presentation was found to require the expression by accessory cells of the Aek-gene product, whereas all Eα allelic molecules were functionally equivalent. These results (a) indicate that the immunoregulatory role of I-region gene products, initially described for molecules selected for their limited number of antigenic epitopes, also applies to complex multiepitopic antigens; (b) illustrate the advantage which results from the diversity of the la molecules expressed by accessory cells for the development of potent immune responses; and (c) suggest that a correlation might exist between the degree of polymorphism of a given family of H-2 allelic molecules and their ability to be used as restriction elements for antigen recognition by T lymphocytes.

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Abbreviations

FCS:

fetal calf serum

Hepes:

N-2-hydroxypiperazine-N′-2 ethanesulfonic acid; in polypeptides

G:

glutamate

L:

lysine

Ø:

phenylalanine

KLH:

keyhole limpet hemocyanin

m. Ab.:

monoclonal antibodies

T cells:

thymus-derived cells

References

  • Burger, R. and Shevach, E. M.: Monoclonal antibodies to guinea pig la antigens. II. Effect on alloantigen-, antigen-, and mitogen-induced T lymphocyte proliferation in vitro. J. Exp. Med. 152: 1011–1023, 1980

    Google Scholar 

  • Cook, R. G., Vitetta, E. S., Uhr, J. W., and Capra, J. D.: Structural studies on the murine la alloantigens. III. Tryptic peptide comparisons of allelic products of the I-E/C sub-region. Mol. Immunol. 16: 29–35, 1979

    Google Scholar 

  • Corradin, G., Erlinger, H. M., and Chiller, J. M.: Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative responses with lymph node cells from primed mice. J. Immunol. 119: 1048–1053, 1977

    Google Scholar 

  • Dorf, M. E. and Benacerraf, B.: Complementation of H-2-linked Ir genes in the mouse. Proc. Natl. Acad. Sci. U.S.A. 72: 3671–3675, 1975

    Google Scholar 

  • Dubreuil, P., Pierres, M., Caillol, D., and Lemonnier, F.: Inhibition of T-cell proliferative responses by monoclonal antibodies reacting with the I-E/Ck subregion product. Immunobiol. 159: 47, 1981

    Google Scholar 

  • Fathman, G. G. and Kimoto, M.: Studies utilizing murine T cell clones: Ir genes, la antigens and MLR stimulating determinants. Immunol. Rev. 54: 57–79, 1981

    Google Scholar 

  • Goding, J. W.: Use of staphylococcal protein A as an immunological reagent. J. Immunol. Methods 20: 241–253, 1978

    Google Scholar 

  • Hodes, R. J., Hatchcock, K. S., and Singer, A.: Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-A k reagent blocks helper T cell recognition of self major histocompatibility complex determinants. J. Exp. Med. 152: 1779–1794, 1980

    Google Scholar 

  • Iványi, D. and Démant, P.: Serological characterization of previously unknown H-2 molecules identified in the products of the K d and D k regions. Immunogenetics 12: 397–408, 1981

    Google Scholar 

  • Jones, P. P., Murphy, D. B., and McDevitt, H. O.: Two-gene control of the expression of a murine la antigen J. Exp. Med. 148: 925–939, 1978

    Google Scholar 

  • Kimoto, M. and Fathman, G. G.: Antigen-reactive T cell clones. I. Transcomplementing hybrid I-Aregion gene products function effectively in antigen presentation. J. Exp. Med. 152: 759–770, 1980

    Google Scholar 

  • Martinez-A. C., Coutinho, A., and Bernabé, R. R.: Hapten specific helper T cells restricted by the 1-E (C) subregion of the MHC. Immunogenetics 10: 299–303, 1980

    Google Scholar 

  • Meo, T., David, G. S., Rijmbeck, A. M., Nabholz, M., Miggiano, V. C., and Shreffler, D. C.: Inhibition of mouse MLR by anti-Ia sera. Transplant. Proc. 7 (Suppl. 1): 127–129, 1975

    Google Scholar 

  • Oi, V. T., Jones, P. P., Goding, J. W., Herzenberg, L. A., and Herzenberg, L. A.: Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. In F. Melchers, M. Potter, N. L. Warner (eds.): Current Topics in Microbiology and Immunology, pp. 115–125, Springer-Verlag, Berlin 1978

    Google Scholar 

  • Pierres, M., Kourilsky, F. M., Rebouah, J. P., Dosseto, M., and Caillol, D.: Distinct epitopes on Ik gene products identified by monoclonal antibodies. Eur. J. Immunol. 10: 950–957, 1980

    Google Scholar 

  • Ruhl, H. and Shevach, E. M.: The effect of alloantisera on antigen-induced T cell proliferation. J. Immunol. 115: 1493–1499, 1975

    Google Scholar 

  • Schwartz, R. H., Fathman, C. H., and Sachs, D. H.: Inhibition of stimulation in murine mixed lymphocyte cultures with an alloantiserum directed against a shared Ia determinant. J. Immunol. 116: 929–935, 1976a

    Google Scholar 

  • Schwartz, R. H., David, C. S., Sachs, D. H., and Paul, W. E.: T lymphocyte-enriched murine peritoneal exudate cells. III. Inhibition of antigen-induced T lymphocyte proliferation with anti-Ia antisera. J. Immunol. 117: 531–540, 1976b

    Google Scholar 

  • Schwartz, R. H., Yano, A., and Paul, W. E.: Interaction between antigen-presenting cells and primed T lymphocytes: An assessment of Ir gene expression in the antigen-presenting cells. Immunol. Rev. 40: 153–180, 1978

    Google Scholar 

  • Schwartz, R. H., Chen, C., and Paul, W. E.: Gene complementation in the T lymphocyte proliferative response to poly (G1u56Lys35Phe9)m. Functional evidence for a restriction element coded for by both the I-A and I-E subregions. Eur. J. Immunol. 10: 708–714, 1980

    Google Scholar 

  • Silver, J.: Trans gene complementation of I-E subregion antigens. J. Immunol. 123: 1423–1425, 1979

    Google Scholar 

  • Sredni, B., Tse, H. Y., and Schwartz, R. H.: Direct cloning and extended culture of antigen-specific MHC-restricted, proliferating T lymphocytes. Nature 283: 581–583, 1980

    Google Scholar 

  • Sredni, B., Matis, L. A., Lerner, E. A., Paul, W. E., and Schwartz, R. H.: Antigen-specific T cell clones restricted to unique F1 major histocompatibility complex determinants. Inhibition of proliferation with a monoclonal anti-Ia antibody. J. Exp. Med. 153: 677–693, 1981

    Google Scholar 

  • Uhr, J. W., Capra, J. D., Vitetta, E. S., and Cook, R. G.: Organization of the immune response genes. Both subunits of murine I-A and I-E/C molecules are encoded within the I region. Science 206: 292–297, 1979

    Google Scholar 

  • Vaz, N. M., Phillips-Quagliata, J. M., Lavine, B. B., and Vaz, E. M.: H-2-linked genetic control of immune responsiveness to ovalbumin and ovomucoid. J. Exp. Med. 134: 1335–1348, 1971

    Google Scholar 

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Dubreuil, P.C., Caillol, D.H. & Lemonnier, F.A. KLH-specific, I-E/C-restricted clones of proliferating T lymphocytes. Immunogenetics 14, 469–479 (1981). https://doi.org/10.1007/BF00350119

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  • DOI: https://doi.org/10.1007/BF00350119

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