Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Oct 1;158(4):1077–1091. doi: 10.1084/jem.158.4.1077

The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product

PMCID: PMC2187386  PMID: 6413636

Abstract

We have examined the role of the murine homologue of Leu-3 T4, L3T4, in recognition of antigen in association with products of the major histocompatibility complex (Ag/MHC) by murine T cell hybridomas. A series of ovalbumin (OVA)/I-Ad-specific T cell hybridomas were ranked in their sensitivity to Ag/I by measuring their ability to respond to low doses of OVA, or their sensitivity to inhibition by anti-I-Ad antibodies. T cell hybridomas with low apparent avidity for OVA/I-Ad, i.e. that did not respond well to low concentrations of OVA and were easily inhibited by anti-I-Ad, were also easily inhibited by anti-L3T4 antibodies. The reverse was true for T cell hybridomas with apparent high avidity for Ag/MHC. We found that the presence of low doses of anti-L3T4 antibodies caused T cell hybridomas to respond less well to low doses of Ag, and to be more easily inhibited by anti-I-Ad antibodies. These results suggested that the role of the L3T4 molecule is to increase the overall avidity of the reaction between T cells and Ag-presenting cells. In support of this idea was the discovery of several L3T4- subclones of one of our L3T4+ T cell hybridomas, D0.11.10. The L3T4- subclones had the same amount of receptor for OVA/I- Ad as their L3T4+ parent, as detected by an anti-receptor monoclonal antibody. The L3T4- subclones, however, responded less well to low doses of OVA, and were more easily inhibited by anti-I-Ad antibodies than their L3T4/ parent. These results showed that the L3T4 molecule was not required for surface expression of, or functional activity of, the T cell receptor for Ag/MHC. The L3T4 molecule did, however, increase the sensitivity with which the T cell reacted with Ag/MHC on Ag-presenting cells.

Full Text

The Full Text of this article is available as a PDF (905.3 KB).

Selected References

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

  1. Bhattacharya A., Dorf M. E., Springer T. A. A shared alloantigenic determinant on Ia antigens encoded by the I-A and I-E subregions: evidence for I region gene duplication. J Immunol. 1981 Dec;127(6):2488–2495. [PubMed] [Google Scholar]
  2. Biddison W. E., Rao P. E., Talle M. A., Goldstein G., Shaw S. Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of cytotoxic T lymphocytes specific for SB antigens. J Exp Med. 1982 Oct 1;156(4):1065–1076. doi: 10.1084/jem.156.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): mechanism of blockade of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions. J Immunol. 1981 Aug;127(2):590–595. [PubMed] [Google Scholar]
  4. Dennert G., Hyman R., Lesley J., Trowbridge I. S. Effects of cytotoxic monoclonal antibody specific for T200 glycoprotein on functional lymphoid cell populations. Cell Immunol. 1980 Aug 1;53(2):350–364. doi: 10.1016/0008-8749(80)90335-4. [DOI] [PubMed] [Google Scholar]
  5. Engleman E. G., Benike C. J., Glickman E., Evans R. L. Antibodies to membrane structures that distinguish suppressor/cytotoxic and helper T lymphocyte subpopulations block the mixed leukocyte reaction in man. J Exp Med. 1981 Jul 1;154(1):193–198. doi: 10.1084/jem.154.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans R. L., Wall D. W., Platsoucas C. D., Siegal F. P., Fikrig S. M., Testa C. M., Good R. A. Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen. Proc Natl Acad Sci U S A. 1981 Jan;78(1):544–548. doi: 10.1073/pnas.78.1.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Haskins K., Kubo R., White J., Pigeon M., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med. 1983 Apr 1;157(4):1149–1169. doi: 10.1084/jem.157.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hollander N., Pillemer E., Weissman I. L. Blocking effect of lyt-2 antibodies on T cell functions. J Exp Med. 1980 Sep 1;152(3):674–687. doi: 10.1084/jem.152.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaufmann Y., Golstein P., Pierres M., Springer T. A., Eshhar Z. LFA-1 but not Lyt-2 is associated with killing activity of cytotoxic T lymphocyte hybridomas. Nature. 1982 Nov 25;300(5890):357–360. doi: 10.1038/300357a0. [DOI] [PubMed] [Google Scholar]
  11. Kim K. J., Kanellopoulos-Langevin C., Merwin R. M., Sachs D. H., Asofsky R. Establishment and characterization of BALB/c lymphoma lines with B cell properties. J Immunol. 1979 Feb;122(2):549–554. [PubMed] [Google Scholar]
  12. Lipscomb M. F., Ben-Sasson S. Z., Tucker T. F., Uhr J. W. Specific binding of T lymphocytes to macrophages IV. Dependence on cations, temperature and cytochalasin B-sensitive mechanisms. Eur J Immunol. 1979 Feb;9(2):119–125. doi: 10.1002/eji.1830090205. [DOI] [PubMed] [Google Scholar]
  13. Lipsky P. E., Rosenthal A. S. Macrophage-lymphocyte interaction. II. Antigen-mediated physical interactions between immune guinea pig lymph node lymphocytes and syngeneic macrophages. J Exp Med. 1975 Jan 1;141(1):138–154. doi: 10.1084/jem.141.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marrack P., Skidmore B., Kappler J. W. Binding of antigen-specific, H-2-restricted T cell hybridomas to antigen-pulsed adherent cell monolayers. J Immunol. 1983 May;130(5):2088–2092. [PubMed] [Google Scholar]
  15. Meuer S. C., Fitzgerald K. A., Hussey R. E., Hodgdon J. C., Schlossman S. F., Reinherz E. L. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med. 1983 Feb 1;157(2):705–719. doi: 10.1084/jem.157.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Meuer S. C., Hussey R. E., Hodgdon J. C., Hercend T., Schlossman S. F., Reinherz E. L. Surface structures involved in target recognition by human cytotoxic T lymphocytes. Science. 1982 Oct 29;218(4571):471–473. doi: 10.1126/science.6981845. [DOI] [PubMed] [Google Scholar]
  17. Meuer S. C., Schlossman S. F., Reinherz E. L. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395–4399. doi: 10.1073/pnas.79.14.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nakayama E., Shiku H., Stockert E., Oettgen H. F., Old L. J. Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1977–1981. doi: 10.1073/pnas.76.4.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reinherz E. L., Schlossman S. F. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. doi: 10.1016/0092-8674(80)90072-0. [DOI] [PubMed] [Google Scholar]
  21. Sarmiento M., Dialynas D. P., Lancki D. W., Wall K. A., Lorber M. I., Loken M. R., Fitch F. W. Cloned T lymphocytes and monoclonal antibodies as probes for cell surface molecules active in T cell-mediated cytolysis. Immunol Rev. 1982;68:135–169. doi: 10.1111/j.1600-065x.1982.tb01063.x. [DOI] [PubMed] [Google Scholar]
  22. Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shinohara N., Hämmerling U., Sachs D. H. Mouse alloantibodies capable of blocking cytotoxic T cell function. II. Further study on the relationship between the blocking antibodies and the products of the Lyt-2 locus. Eur J Immunol. 1980 Aug;10(8):589–594. doi: 10.1002/eji.1830100804. [DOI] [PubMed] [Google Scholar]
  24. Spits H., Borst J., Terhorst C., de Vries J. E. The role of T cell differentiation markers in antigen-specific and lectin-dependent cellular cytotoxicity mediated by T8+ and T4+ human cytotoxic T cell clones directed at class I and class II MHC antigens. J Immunol. 1982 Oct;129(4):1563–1569. [PubMed] [Google Scholar]
  25. Swain S. L., Dutton R. W., Schwab R., Yamamoto J. Xenogeneic human anti-mouse T cell responses are due to the activity of the same functional T cell subsets responsible for allospecific and major histocompatibility complex-restricted responses. J Exp Med. 1983 Feb 1;157(2):720–729. doi: 10.1084/jem.157.2.720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Swain S. L. Significance of Lyt phenotypes: Lyt2 antibodies block activities of T cells that recognize class 1 major histocompatibility complex antigens regardless of their function. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7101–7105. doi: 10.1073/pnas.78.11.7101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Trowbridge I. S., Omary M. B. Molecular complexity of leukocyte surface glycoproteins related to the macrophage differentiation antigen Mac-1. J Exp Med. 1981 Nov 1;154(5):1517–1524. doi: 10.1084/jem.154.5.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Walker E., Warner N. L., Chesnut R., Kappler J., Marrack P. Antigen-specific. I region-restricted interactions in vitro between tumor cell lines and T cell hybridomas. J Immunol. 1982 May;128(5):2164–2169. [PubMed] [Google Scholar]
  29. Ziegler K., Unanue E. R. The specific binding of Listeria monocytogenes-immune T lymphocytes to macrophages. I. Quantitation and role of H-2 gene products. J Exp Med. 1979 Nov 1;150(5):1143–1160. doi: 10.1084/jem.150.5.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES