Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Apr 1;88(7):2623–2627. doi: 10.1073/pnas.88.7.2623

Adhesion versus coreceptor function of CD4 and CD8: role of the cytoplasmic tail in coreceptor activity.

M C Miceli 1, P von Hoegen 1, J R Parnes 1
PMCID: PMC51290  PMID: 1901411

Abstract

CD4 and CD8 play an important role in T-cell recognition and activation; however, their mechanisms of action are not well understood. We compare the effects of expressing CD4 and CD8 alpha either individually or together in a class II-restricted T-cell hybridoma. We also compare the effects of expressing truncated forms of CD4 or CD8 alpha that do not have a cytoplasmic tail and thus do not associate with the T-cell-specific tyrosine kinase p56lck, which has been implicated in T-cell activation. We demonstrate that, although CD4 and CD8 alpha can specifically enhance interleukin 2 secretion, maximal potentiation occurs with expression of CD4, which, unlike CD8, can bind to the same major histocompatibility complex protein as the T-cell receptor. Our data further indicate that the cytoplasmic tail and/or the associated p56lck are primarily significant for interleukin 2 secretion by the hybridomas we have examined when CD4 or CD8 can bind to the same major histocompatibility complex ligand as the T-cell receptor.

Full text

PDF
2623

Selected References

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

  1. Anderson P., Blue M. L., Morimoto C., Schlossman S. F. Cross-linking of T3 (CD3) with T4 (CD4) enhances the proliferation of resting T lymphocytes. J Immunol. 1987 Aug 1;139(3):678–682. [PubMed] [Google Scholar]
  2. Anderson P., Blue M. L., Schlossman S. F. Comodulation of CD3 and CD4. Evidence for a specific association between CD4 and approximately 5% of the CD3:T cell receptor complexes on helper T lymphocytes. J Immunol. 1988 Mar 15;140(6):1732–1737. [PubMed] [Google Scholar]
  3. Ballhausen W. G., Reske-Kunz A. B., Tourvieille B., Ohashi P. S., Parnes J. R., Mak T. W. Acquisition of an additional antigen specificity after mouse CD4 gene transfer into a T helper hybridoma. J Exp Med. 1988 Apr 1;167(4):1493–1498. doi: 10.1084/jem.167.4.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Connolly J. M., Hansen T. H., Ingold A. L., Potter T. A. Recognition by CD8 on cytotoxic T lymphocytes is ablated by several substitutions in the class I alpha 3 domain: CD8 and the T-cell receptor recognize the same class I molecule. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2137–2141. doi: 10.1073/pnas.87.6.2137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dembić Z., Haas W., Zamoyska R., Parnes J., Steinmetz M., von Boehmer H. Transfection of the CD8 gene enhances T-cell recognition. Nature. 1987 Apr 2;326(6112):510–511. doi: 10.1038/326510a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Doyle C., Strominger J. L. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987 Nov 19;330(6145):256–259. doi: 10.1038/330256a0. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Gabert J., Langlet C., Zamoyska R., Parnes J. R., Schmitt-Verhulst A. M., Malissen B. Reconstitution of MHC class I specificity by transfer of the T cell receptor and Lyt-2 genes. Cell. 1987 Aug 14;50(4):545–554. doi: 10.1016/0092-8674(87)90027-4. [DOI] [PubMed] [Google Scholar]
  10. Gallagher P. F., Fazekas de St Groth B., Miller J. F. CD4 and CD8 molecules can physically associate with the same T-cell receptor. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10044–10048. doi: 10.1073/pnas.86.24.10044. [DOI] [PMC free article] [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. Goldstein S. A., Mescher M. F. T cell recognition of nonpolymorphic determinants on H-2 class I molecules. J Immunol. 1988 Jun 1;140(11):3707–3711. [PubMed] [Google Scholar]
  13. Gunning P., Leavitt J., Muscat G., Ng S. Y., Kedes L. A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831–4835. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hsi E. D., Siegel J. N., Minami Y., Luong E. T., Klausner R. D., Samelson L. E. T cell activation induces rapid tyrosine phosphorylation of a limited number of cellular substrates. J Biol Chem. 1989 Jun 25;264(18):10836–10842. [PubMed] [Google Scholar]
  15. Janeway C. A., Jr, Rojo J., Saizawa K., Dianzani U., Portoles P., Tite J., Haque S., Jones B. The co-receptor function of murine CD4. Immunol Rev. 1989 Jun;109:77–92. doi: 10.1111/j.1600-065x.1989.tb00020.x. [DOI] [PubMed] [Google Scholar]
  16. Jones B., Khavari P. A., Conrad P. J., Janeway C. A., Jr Differential effects of antibodies to Lyt-2 and L3T4 on cytolysis by cloned, Ia-restricted T cells expressing both proteins. J Immunol. 1987 Jul 15;139(2):380–384. [PubMed] [Google Scholar]
  17. June C. H., Fletcher M. C., Ledbetter J. A., Samelson L. E. Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation. J Immunol. 1990 Mar 1;144(5):1591–1599. [PubMed] [Google Scholar]
  18. Letourneur F., Gabert J., Cosson P., Blanc D., Davoust J., Malissen B. A signaling role for the cytoplasmic segment of the CD8 alpha chain detected under limiting stimulatory conditions. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2339–2343. doi: 10.1073/pnas.87.6.2339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liaw C. W., Zamoyska R., Parnes J. R. Structure, sequence, and polymorphism of the Lyt-2 T cell differentiation antigen gene. J Immunol. 1986 Aug 1;137(3):1037–1043. [PubMed] [Google Scholar]
  20. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  21. Norment A. M., Salter R. D., Parham P., Engelhard V. H., Littman D. R. Cell-cell adhesion mediated by CD8 and MHC class I molecules. Nature. 1988 Nov 3;336(6194):79–81. doi: 10.1038/336079a0. [DOI] [PubMed] [Google Scholar]
  22. O'Rourke A. M., Rogers J., Mescher M. F. Activated CD8 binding to class I protein mediated by the T-cell receptor results in signalling. Nature. 1990 Jul 12;346(6280):187–189. doi: 10.1038/346187a0. [DOI] [PubMed] [Google Scholar]
  23. Parnes J. R., von Hoegen P., Miceli M. C., Zamoyska R. Role of CD4 and CD8 in enhancing T-cell responses to antigen. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 2):649–655. doi: 10.1101/sqb.1989.054.01.076. [DOI] [PubMed] [Google Scholar]
  24. Potter T. A., Rajan T. V., Dick R. F., 2nd, Bluestone J. A. Substitution at residue 227 of H-2 class I molecules abrogates recognition by CD8-dependent, but not CD8-independent, cytotoxic T lymphocytes. Nature. 1989 Jan 5;337(6202):73–75. doi: 10.1038/337073a0. [DOI] [PubMed] [Google Scholar]
  25. Ratnofsky S. E., Peterson A., Greenstein J. L., Burakoff S. J. Expression and function of CD8 in a murine T cell hybridoma. J Exp Med. 1987 Dec 1;166(6):1747–1757. doi: 10.1084/jem.166.6.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Reske-Kunz A. B., Rüde E. Insulin-specific T cell hybridomas derived from (H-2b x H-2k)F1 mice preferably employ F1-unique restriction elements for antigen recognition. Eur J Immunol. 1985 Oct;15(10):1048–1054. doi: 10.1002/eji.1830151017. [DOI] [PubMed] [Google Scholar]
  27. Rojo J. M., Saizawa K., Janeway C. A., Jr Physical association of CD4 and the T-cell receptor can be induced by anti-T-cell receptor antibodies. Proc Natl Acad Sci U S A. 1989 May;86(9):3311–3315. doi: 10.1073/pnas.86.9.3311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rosenstein Y., Ratnofsky S., Burakoff S. J., Herrmann S. H. Direct evidence for binding of CD8 to HLA class I antigens. J Exp Med. 1989 Jan 1;169(1):149–160. doi: 10.1084/jem.169.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rudd C. E., Trevillyan J. M., Dasgupta J. D., Wong L. L., Schlossman S. F. The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5190–5194. doi: 10.1073/pnas.85.14.5190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Salter R. D., Benjamin R. J., Wesley P. K., Buxton S. E., Garrett T. P., Clayberger C., Krensky A. M., Norment A. M., Littman D. R., Parham P. A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2. Nature. 1990 May 3;345(6270):41–46. doi: 10.1038/345041a0. [DOI] [PubMed] [Google Scholar]
  31. Salter R. D., Norment A. M., Chen B. P., Clayberger C., Krensky A. M., Littman D. R., Parham P. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature. 1989 Mar 23;338(6213):345–347. doi: 10.1038/338345a0. [DOI] [PubMed] [Google Scholar]
  32. Samelson L. E., Patel M. D., Weissman A. M., Harford J. B., Klausner R. D. Antigen activation of murine T cells induces tyrosine phosphorylation of a polypeptide associated with the T cell antigen receptor. Cell. 1986 Sep 26;46(7):1083–1090. doi: 10.1016/0092-8674(86)90708-7. [DOI] [PubMed] [Google Scholar]
  33. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  34. Shaw A. S., Amrein K. E., Hammond C., Stern D. F., Sefton B. M., Rose J. K. The lck tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain. Cell. 1989 Nov 17;59(4):627–636. doi: 10.1016/0092-8674(89)90008-1. [DOI] [PubMed] [Google Scholar]
  35. Sleckman B. P., Peterson A., Foran J. A., Gorga J. C., Kara C. J., Strominger J. L., Burakoff S. J., Greenstein J. L. Functional analysis of a cytoplasmic domain-deleted mutant of the CD4 molecule. J Immunol. 1988 Jul 1;141(1):49–54. [PubMed] [Google Scholar]
  36. 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]
  37. Turner J. M., Brodsky M. H., Irving B. A., Levin S. D., Perlmutter R. M., Littman D. R. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell. 1990 Mar 9;60(5):755–765. doi: 10.1016/0092-8674(90)90090-2. [DOI] [PubMed] [Google Scholar]
  38. Veillette A., Bookman M. A., Horak E. M., Bolen J. B. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988 Oct 21;55(2):301–308. doi: 10.1016/0092-8674(88)90053-0. [DOI] [PubMed] [Google Scholar]
  39. Veillette A., Bookman M. A., Horak E. M., Samelson L. E., Bolen J. B. Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck. Nature. 1989 Mar 16;338(6212):257–259. doi: 10.1038/338257a0. [DOI] [PubMed] [Google Scholar]
  40. Zamoyska R., Derham P., Gorman S. D., von Hoegen P., Bolen J. B., Veillette A., Parnes J. R. Inability of CD8 alpha' polypeptides to associate with p56lck correlates with impaired function in vitro and lack of expression in vivo. Nature. 1989 Nov 16;342(6247):278–281. doi: 10.1038/342278a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES