Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1977 Sep 1;146(3):828–843. doi: 10.1084/jem.146.3.828

Antigen presentation in the murine T-lymphocyte proliferative response. I. Requirement for genetic identity at the major histocompatibility complex

A Yano, RH Schwartz, WE Paul
PMCID: PMC2180782  PMID: 70497

Abstract

A method is described for stimulating proliferation in primed populations of murine T lymphocytes using antigen bound to mitomycin-C-treated spleen cells. This form of antigen presentation appears to be an active process because heat-killed spleen cells are ineffective, and because genetic similarity at the major histocompatibility complex (MHC) between the responder T cells and the presenting spleen cells is required for effective interactions. At all times examined, from day 3 to day 6 of the proliferative response, syngeneic spleen cells presented antigen better to peritoneal exudate T-lymphocyte-enriched cells (PETLES) than semisyngeneic F(1) spleen cells, which in turn could present antigen better than totally allogeneic spleen cells. Spleen cell mixing experiments demonstrated that these genetic restrictions were not the result of suppression by the ongoing mixed lymphocyte reactions (MLR) in the allogeneic and F(1) cases. Furthermore, incompatibility at the Mls locus generated a strong MLR but failed to prevent antigen presentation if the spleen cells and PETLES were compatible. Genetic mapping studies demonstrated that compatibility at only the I-A subregion of the MHC was sufficient for effective presentation of the antigen, dinitrophenylated ovalbumin. Compatibility at only the K region, or the K and D regions was not sufficient. These results support the concept that functional activation of primed, proliferating T lymphocytes requires the participation of gene products coded for by the I region of the MHC. This conclusion is consistent with a growing body of evidence which suggests that most T cells recognize antigen in association with MHC gene products.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bevan M. J. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J Exp Med. 1975 Dec 1;142(6):1349–1364. doi: 10.1084/jem.142.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cosenza H., Leserman L. D. Cell interactions in antibody formation in vitro. I. Role of the third cell in the in vitro response of spleen cells to erythrocyte antigens. J Immunol. 1972 Feb;108(2):418–424. [PubMed] [Google Scholar]
  3. Doherty P. C., Zinkernagel R. M. A biological role for the major histocompatibility antigens. Lancet. 1975 Jun 28;1(7922):1406–1409. doi: 10.1016/s0140-6736(75)92610-0. [DOI] [PubMed] [Google Scholar]
  4. Erb P., Feldmann M. The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens. J Exp Med. 1975 Aug 1;142(2):460–472. doi: 10.1084/jem.142.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Germain R. N., Dorf M. E., Benacerraf B. Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor. J Exp Med. 1975 Oct 1;142(4):1023–1028. doi: 10.1084/jem.142.4.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Janeway C. A., Wigzell H., Binz H. Two different VH gene products make up the T-cell receptors. Scand J Immunol. 1976;5(9):993–1001. doi: 10.1111/j.1365-3083.1976.tb03051.x. [DOI] [PubMed] [Google Scholar]
  7. Kappler J. W., Marrack P. C. Helper T cells recognise antigen and macrophage surface components simultaneously. Nature. 1976 Aug 26;262(5571):797–799. doi: 10.1038/262797a0. [DOI] [PubMed] [Google Scholar]
  8. Katz D. H., Graves M., Dorf M. E., Dimuzio H., Benacerraf B. 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. 1975 Jan 1;141(1):263–268. doi: 10.1084/jem.141.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Katz D. H., Hamaoka T., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates. J Exp Med. 1973 Jun 1;137(6):1405–1418. doi: 10.1084/jem.137.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Katz D. H., Unanue E. R. Critical role of determinant presentation in the induction of specific responses in immunocompetent lymphocytes. J Exp Med. 1973 Apr 1;137(4):967–990. doi: 10.1084/jem.137.4.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5095–5098. doi: 10.1073/pnas.72.12.5095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mitchison N. A. The immunogenic capacity of antigen taken up by peritoneal exudate cells. Immunology. 1969 Jan;16(1):1–14. [PMC free article] [PubMed] [Google Scholar]
  13. Paul W. E., Benacerraf B. Functional specificity of thymus- dependent lymphocytes. Science. 1977 Mar 25;195(4284):1293–1300. doi: 10.1126/science.320663. [DOI] [PubMed] [Google Scholar]
  14. Pierce C. W., Kapp J. A., Benacerraf B. Regulation by the H-2 gene complex of macrophage-lymphoid cell interactions in secondary antibody responses in vitro. J Exp Med. 1976 Aug 1;144(2):371–381. doi: 10.1084/jem.144.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Roos D., Loos J. A. Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. I. Stimulation by phytohaemagglutinin. Biochim Biophys Acta. 1970 Dec 29;222(3):565–582. doi: 10.1016/0304-4165(70)90182-0. [DOI] [PubMed] [Google Scholar]
  16. Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schrader J. W., Edelman G. M. Participation of the H-2 antigens of tumor cells in their lysis by syngeneic T cells. J Exp Med. 1976 Mar 1;143(3):601–614. doi: 10.1084/jem.143.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schwartz R. H., Horton C. L., Paul W. E. T-lymphocyte-enriched murine peritoneal exudate cells. IV. Genetic control of cross-stimulation at the T-cell level. J Exp Med. 1977 Feb 1;145(2):327–343. doi: 10.1084/jem.145.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schwartz R. H., Jackson L., Paul W. E. T lymphocyte-enriched murine peritoneal exudate cells. I. A reliable assay for antigen-induced T lymphocyte proliferation. J Immunol. 1975 Nov;115(5):1330–1338. [PubMed] [Google Scholar]
  20. Schwartz R. H., Paul W. E. T-lymphocyte-enriched murine peritoneal exudate cells. II. Genetic control of antigen-induced T-lymphocyte proliferation. J Exp Med. 1976 Mar 1;143(3):529–540. doi: 10.1084/jem.143.3.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shevach E. M., Rosenthal A. S. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response. J Exp Med. 1973 Nov 1;138(5):1213–1229. doi: 10.1084/jem.138.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thomas D. W., Shevach E. M. Nature of the antigenic complex recognized by T lymphocytes. I. Analysis with an in vitro primary response to soluble protein antigens. J Exp Med. 1976 Nov 2;144(5):1263–1273. doi: 10.1084/jem.144.5.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Thomas D. W., Shevach E. M. Nature of the antigenic complex recognized by T lymphocytes: specific sensitization by antigens associated with allogeneic macrophages. Proc Natl Acad Sci U S A. 1977 May;74(5):2104–2108. doi: 10.1073/pnas.74.5.2104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Waldron J. A., Jr, Horn R. G., Rosenthal A. S. Antigen-induced proliferation of guinea pig lymphocytes in vitro: functional aspects of antigen handling by macrophages. J Immunol. 1974 Feb;112(2):746–755. [PubMed] [Google Scholar]
  25. Zinkernagel R. M., Doherty P. C. H-2 compatability requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificities are associated with structures coded for in H-2K or H-2D;. J Exp Med. 1975 Jun 1;141(6):1427–1436. doi: 10.1084/jem.141.6.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES