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. 1988 Aug;85(15):5629–5633. doi: 10.1073/pnas.85.15.5629

The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.

D Gay 1, S Buus 1, J Pasternak 1, J Kappler 1, P Marrack 1
PMCID: PMC281813  PMID: 3261012

Abstract

The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; Ia) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigen-presenting cell (APC) and functions either by enhancing interaction between the T cell and the APC, or conversely, by transducing negative signals to the T cell. To address this hypothesis, we have made use of sublines from an unusual T hybrid that is class I MHC restricted but also CD4+. By incorporating purified MHC proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4- variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target.

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Selected References

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

  1. Bank I., Chess L. Perturbation of the T4 molecule transmits a negative signal to T cells. J Exp Med. 1985 Oct 1;162(4):1294–1303. doi: 10.1084/jem.162.4.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bekoff M., Kakiuchi T., Grey H. M. Accessory cell function in the Con A response: role of Ia-positive and Ia-negative accessory cells. J Immunol. 1985 Mar;134(3):1337–1342. [PubMed] [Google Scholar]
  3. 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]
  4. Blackman M., Yagüe J., Kubo R., Gay D., Coleclough C., Palmer E., Kappler J., Marrack P. The T cell repertoire may be biased in favor of MHC recognition. Cell. 1986 Nov 7;47(3):349–357. doi: 10.1016/0092-8674(86)90591-x. [DOI] [PubMed] [Google Scholar]
  5. Brian A. A., McConnell H. M. Allogeneic stimulation of cytotoxic T cells by supported planar membranes. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6159–6163. doi: 10.1073/pnas.81.19.6159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Buus S., Sette A., Colon S. M., Jenis D. M., Grey H. M. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell. 1986 Dec 26;47(6):1071–1077. doi: 10.1016/0092-8674(86)90822-6. [DOI] [PubMed] [Google Scholar]
  7. Coeshott C. M., Chesnut R. W., Kubo R. T., Grammer S. F., Jenis D. M., Grey H. M. Ia-specific mixed leukocyte reactive T cell hybridomas: analysis of their specificity by using purified class II MHC molecules in synthetic membrane system. J Immunol. 1986 Apr 15;136(8):2832–2838. [PubMed] [Google Scholar]
  8. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  9. Fazekas de St Groth B., Gallagher P. F., Miller J. F. Involvement of Lyt-2 and L3T4 in activation of hapten-specific Lyt-2+ L3T4+ T-cell clones. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2594–2598. doi: 10.1073/pnas.83.8.2594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gay D., Coeshott C., Golde W., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells. IX. Role of accessory molecules in recognition of antigen plus isolated IA. J Immunol. 1986 Mar 15;136(6):2026–2032. [PubMed] [Google Scholar]
  11. Gay D., Maddon P., Sekaly R., Talle M. A., Godfrey M., Long E., Goldstein G., Chess L., Axel R., Kappler J. Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature. 1987 Aug 13;328(6131):626–629. doi: 10.1038/328626a0. [DOI] [PubMed] [Google Scholar]
  12. Golstein P., Goridis C., Schmitt-Verhulst A. M., Hayot B., Pierres A., van Agthoven A., Kaufmann Y., Eshhar Z., Pierres M. Lymphoid cell surface interaction structures detected using cytolysis-inhibiting monoclonal antibodies. Immunol Rev. 1982;68:5–42. doi: 10.1111/j.1600-065x.1982.tb01058.x. [DOI] [PubMed] [Google Scholar]
  13. Greenstein J. L., Kappler J., Marrack P., Burakoff S. J. The role of L3T4 in recognition of Ia by a cytotoxic, H-2Dd-specific T cell hybridoma. J Exp Med. 1984 Apr 1;159(4):1213–1224. doi: 10.1084/jem.159.4.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Kappler J., Kubo R., Haskins K., White J., Marrack P. The mouse T cell receptor: comparison of MHC-restricted receptors on two T cell hybridomas. Cell. 1983 Oct;34(3):727–737. doi: 10.1016/0092-8674(83)90529-9. [DOI] [PubMed] [Google Scholar]
  16. Katz D. H., Benacerraf B. The function and interrelationships of T-cell receptors, Ir genes and other histocompatibility gene products. Transplant Rev. 1975;22:175–195. doi: 10.1111/j.1600-065x.1975.tb01559.x. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. Marrack P., Endres R., Shimonkevitz R., Zlotnik A., Dialynas D., Fitch F., Kappler J. The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product. J Exp Med. 1983 Oct 1;158(4):1077–1091. doi: 10.1084/jem.158.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2. J Immunol. 1980 Mar;124(3):1301–1307. [PubMed] [Google Scholar]
  21. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Saizawa K., Rojo J., Janeway C. A., Jr Evidence for a physical association of CD4 and the CD3:alpha:beta T-cell receptor. Nature. 1987 Jul 16;328(6127):260–263. doi: 10.1038/328260a0. [DOI] [PubMed] [Google Scholar]
  23. Sleckman B. P., Peterson A., Jones W. K., Foran J. A., Greenstein J. L., Seed B., Burakoff S. J. Expression and function of CD4 in a murine T-cell hybridoma. Nature. 1987 Jul 23;328(6128):351–353. doi: 10.1038/328351a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Watts T. H., Brian A. A., Kappler J. W., Marrack P., McConnell H. M. Antigen presentation by supported planar membranes containing affinity-purified I-Ad. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7564–7568. doi: 10.1073/pnas.81.23.7564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weyand C. M., Goronzy J., Fathman C. G. Modulation of CD4 by antigenic activation. J Immunol. 1987 Mar 1;138(5):1351–1354. [PubMed] [Google Scholar]
  27. Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
  28. 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]

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