Abstract
Twenty-nine randomly chosen, soluble antigens, many of them highly complex, were used to immunize mice of two strains, C3H and B10.RIII. Lymphnode cells from the immunized mice were restimulated in vitro with the priming antigens and the proliferative response of the cells was determined. Both strains were responders to 28 of 29 antigens. Eight antigens were then used to immunize 11 congenic strains carrying different H-2 haplotypes, and the T-cell proliferative responses of these strains were determined. Again, all the strains responded to seven of the eight antigens. These experiments were then repeated, but this time -antibodies specific for the A (AαAβ) or E (EαEβ) molecules were added to the culture to block the in vitro responsiveness. In all but one of the responses, inhibition with both A-specific and E-specific antibodies was observed. The response to one antigen (Blastoinyces) was exceptional in that some strains were nonresponders to this antigen. Furthermore, the response in the responder strains was blocked with A-specific, but not with E-specific, antibodies. The study demonstrates that responses to antigens not controlled by Irr genes nevertheless require participation of class II Mhc molecules. In contrast to Ir gene-controlled responses involving either the A- or the E-molecule controlling loci (but never both), the responses not Ir-controlled involve participation of both A- and E-controlling loci. The lack of Ir-gene control is probably the result of complexity of the responses to multiple determinants. There is thus no principal difference between responses controlled and those not controlled by Ir genes: both types involve the recognition of the antigen, in the context of Mhc molecules.
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Abbreviations
- A:
-
class II MHC molecule consisting of the Aα and Aβ chains
- ADH:
-
alcohol dehydrogenase
- APC:
-
antigen-presenting cell
- cpm:
-
counts per minute
- E:
-
class II Mhc molecule onsisting of the Eα and Aβ chains
- Ir :
-
immune response
- KLH:
-
key-hole limpet hemocyanin
- Mhc:
-
major histocompatibility complex
- PBS:
-
phosphate buffered salt solution
- SD:
-
standard deviation
- SI:
-
stimulation index
- SN:
-
supernatant of Sendai-virus preparation
References
Baxevanis, C. N., Wernet, D., Nagy, Z. A., Maurer, P. H., and Klein, J.: Genetic control of T-cell proliferative responses to poly(glu40ala60) and poly(glu51lys34tyr15): subregion-specific inhibition of the responses with monoclonal Ia antibodies. Immunogenetics 11: 617–628, 1980
Baxevanis, C. N., Nagy, Z. A., and Klein, J.: A novel type of T-T cell interaction removes the requirement for I-B region in the H-2 complex. Proc. Natl. Acad. Sci. U.S.A. 78: 3809–3813, 1981 Benacerraf, B. and McDevitt, H. O.: Histocompatibility-linked immune response genes. Science 175: 273–279, 1972
Corradin, G., Edinger, H. M., and Chiller, J. M.: Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice. J. Immunol. 119: 1048–1053, 1977
Dubriel, P. C., Caillol, D. H., and Lemonier, F. A.: KLH-specific, I-E/C-restricted clones of proliferating T lymphocytes. Immunogenetics 14: 469–479, 1981
Hosaka, Y. and Shinizu, Y. K.: Artificial assembly of envelope particles of Sendai virus. I. Assembly of hemolytic and fusion factors from envelopes solubilized by nonidet P40. Virology 49: 627–639, 1972
Ishii, N., Baxevanis, C. N., Nagy, Z. A., and Klein, J.: Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains. J. Exp. Med. 154: 978–982, 1981
Jones, P. P., Murphy, D. B., and McDevitt, H. O.: Two-gene control of the expression of murine Ia antigen. J. Exp. Med. 148: 925–933, 1978
Koszinowski, U., Getwing, M.-J., and Waterfield, M.: T-cell cytotoxicity in the absence of viral protein synthesis in target cells. Nature 267: 160–163, 1977
Kreo, C. J. and David, C. S.: Genetics of immune response: a survey. CRC Crit. Rev. Immunol. 5: 211–257, 1981
Laemmli, U. K.: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685, 1970
Lemke, H., Hämmerling, G.J., and Hämmerling, U.: Fine specificity analysis with monoclonal antibodies of antigens controlled by the major histocompatibility complex and by the Qa/TL region in mice. Immunol. Rev. 47: 175–206, 1979
Lerner, E. A., Matis, L. A., Janeway, Jr., C. A., Jones, P. P., Schwartz, R. H., and Murphy, D. B.: Monoclonal antibody against an Ir gene product? J. Exp. Med. 152: 1085–1101, 1980
Longo, D. L. and Schwartz, R. H.: Inhibition of antigen-induced proliferation of T cells from radiationinduced bone marrow chimeras by a monoclonal antibody directed against an Ia determinant on the antigen-presenting cell. Proc. Natl. Acad. Sci. U.S.A. 78: 514–518, 1981
McDevitt, H. O. and Chinitz, A.: Genetic control of the antibody response: relationship between immune response and histocompatibility (H-2) type. Science 163: 1207–1208, 1968
McDevitt, H. O. and Sela, M.: Genetic control of the antibody response. I. Demonstration of determinant-specific differences in response to synthetic polypeptide antigens in two strains of inbred mice. J. Exp. Med. 122: 517–531, 1965
Nagy, Z. A., Baxevanis, C. N., Ishii, N., and Klein, J.: Ia antigens as restriction molecules in Ir-gene controlled T-cell proliferation. Immunol. Rev. 60: 59–83, 1981
Nepom, J. T., Benacerraf, B., and Germain, R. N.: Analysis of Ir gene function using monoclonal antibodies: independent regulation of GAT and GLPhe T cell response by I-A and I-E subregion products on a single accessory cell population. J. Immunol. 127: 31–34, 1981
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. Curr. Top. Microbiol. Immunol. 81: 115–129, 1978
Ozato, K., Mayer, N., and Sachs, D. H.: Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J. Immunol. 124: 533–540, 1980
Ryder, L.P., Andersen, E., and Svejgaard, A.: HLA and Disease Registry. Third Report. Munskgaard, Copenhagen. 1979
Schwartz, R. H. and Paul, W. E.: T-lymphocyte-enriched murine peritoneal exudate cells. II. Genetic control of antigen-induced T-lymphocyte proliferation. J. Exp. Med. 143: 529–540, 1976
Shevach, E. M., Paul, W. E., and Green, I.: Histocompatibility-linked immune response gene function in guinea pigs. Specific inhibition of antigen-induced proliferation by alloantisera. J. Exp. Med. 136: 1207–1221, 1972
Shigeta, M. and Fathman, C. G.: I-region genetic restrictions imposed upon the recognition of KLH by murine T-cell clones. Immunogenetics 14: 415–422, 1981
Sprent, J., Lerner, E. A., Bruce, J., and Symington, F. W.: Inhibition of T cell activation in vivo with mixtures of monoclonal antibodies specific for I-A and I-A/E molecules. J. Exp. Med. 154: 188–192, 1981
Zinkernagel, R. M. and Doherty, P. C.: Restriction of an in vitro T cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or simiallogeneic system. Nature 248: 701–702, 1974
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Marušić, M., Nagy, Z.A., Koszinowski, U. et al. Involvement of Mhc Loci in immune responses that are not Ir-gene-controlled. Immunogenetics 16, 471–483 (1982). https://doi.org/10.1007/BF00372105
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DOI: https://doi.org/10.1007/BF00372105