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. 1987 Aug;84(16):5888–5892. doi: 10.1073/pnas.84.16.5888

Coclustering of CD4 (L3T4) molecule with the T-cell receptor is induced by specific direct interaction of helper T cells and antigen-presenting cells.

A Kupfer, S J Singer, C A Janeway Jr, S L Swain
PMCID: PMC298968  PMID: 2956608

Abstract

Blocking studies with monoclonal antibodies have suggested that helper T cell recognition and triggering involve the CD4 (L3T4) accessory molecule as well as the T-cell receptor (TCR) that is linked to the T3 complex. We have investigated the surface distribution of L3T4 and TCR during the direct interaction of a cloned murine helper T-cell line with an antigen-presenting B-cell line. Using immunofluorescence microscopy, we show that in 1:1 cell couples formed between the two cells, in which a specific interaction can be demonstrated, the L3T4 and the TCR become redistributed on the T-cell surface so that they are concentrated in the cell-cell contact region. This coclustering of L3T4 with TCR occurs only when the relevant antigen and appropriate major histocompatibility class II molecules are presented to the T cell, and it therefore requires the specific interaction of the TCR with its complex ligand on the antigen-presenting cell.

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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. Bell G. I., Dembo M., Bongrand P. Cell adhesion. Competition between nonspecific repulsion and specific bonding. Biophys J. 1984 Jun;45(6):1051–1064. doi: 10.1016/S0006-3495(84)84252-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burridge K., Connell L. A new protein of adhesion plaques and ruffling membranes. J Cell Biol. 1983 Aug;97(2):359–367. doi: 10.1083/jcb.97.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  5. Emmrich F., Strittmatter U., Eichmann K. Synergism in the activation of human CD8 T cells by cross-linking the T-cell receptor complex with the CD8 differentiation antigen. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8298–8302. doi: 10.1073/pnas.83.21.8298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Haskins K., Hannum C., White J., Roehm N., Kubo R., Kappler J., Marrack P. The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype. J Exp Med. 1984 Aug 1;160(2):452–471. doi: 10.1084/jem.160.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kappler J., White J., Wegmann D., Mustain E., Marrack P. Antigen presentation by Ia+ B cell hybridomas to H-2-restricted T cell hybridomas. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3604–3607. doi: 10.1073/pnas.79.11.3604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kaye J., Janeway C. A., Jr The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T cell clone blocks activation by either allogeneic Ia or antigen and self-Ia. J Exp Med. 1984 May 1;159(5):1397–1412. doi: 10.1084/jem.159.5.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaye J., Porcelli S., Tite J., Jones B., Janeway C. A., Jr Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells. J Exp Med. 1983 Sep 1;158(3):836–856. doi: 10.1084/jem.158.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Knapp M. R., Severinson-Gronowicz E., Schröder J., Strober S. Characterization of a spontaneous murine B cell leukemia (BCL1). II. Tumor cell proliferation and IgM secretion after stimulation by LPS. J Immunol. 1979 Sep;123(3):1000–1006. [PubMed] [Google Scholar]
  12. Kupfer A., Singer S. J., Dennert G. On the mechanism of unidirectional killing in mixtures of two cytotoxic T lymphocytes. Unidirectional polarization of cytoplasmic organelles and the membrane-associated cytoskeleton in the effector cell. J Exp Med. 1986 Mar 1;163(3):489–498. doi: 10.1084/jem.163.3.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kupfer A., Swain S. L., Janeway C. A., Jr, Singer S. J. The specific direct interaction of helper T cells and antigen-presenting B cells. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6080–6083. doi: 10.1073/pnas.83.16.6080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kupfer A., Swain S. L., Singer S. J. The specific direct interaction of helper T cells and antigen-presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells. J Exp Med. 1987 Jun 1;165(6):1565–1580. doi: 10.1084/jem.165.6.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McCloskey M. A., Poo M. M. Contact-induced redistribution of specific membrane components: local accumulation and development of adhesion. J Cell Biol. 1986 Jun;102(6):2185–2196. doi: 10.1083/jcb.102.6.2185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oettgen H. C., Pettey C. L., Maloy W. L., Terhorst C. A T3-like protein complex associated with the antigen receptor on murine T cells. Nature. 1986 Mar 20;320(6059):272–275. doi: 10.1038/320272a0. [DOI] [PubMed] [Google Scholar]
  17. Rupp F., Brecher J., Giedlin M. A., Mosmann T., Zinkernagel R. M., Hengartner H., Joho R. H. T-cell antigen receptors with identical variable regions but different diversity and joining region gene segments have distinct specificities but cross-reactive idiotypes. Proc Natl Acad Sci U S A. 1987 Jan;84(1):219–222. doi: 10.1073/pnas.84.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Saizawa K., Haque S., Jones B., Rojo J., Tite J. P., Kaye J., Janeway C. A., Jr The L3T4 molecule is part of the helper T-cell antigen/Ia recognition complex. Ann Inst Pasteur Immunol. 1987 Jan-Feb;138(1):138–143. doi: 10.1016/s0769-2625(87)80105-8. [DOI] [PubMed] [Google Scholar]
  19. Staerz U. D., Rammensee H. G., Benedetto J. D., Bevan M. J. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed] [Google Scholar]
  20. 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]
  21. Swain S. L. T cell subsets and the recognition of MHC class. Immunol Rev. 1983;74:129–142. doi: 10.1111/j.1600-065x.1983.tb01087.x. [DOI] [PubMed] [Google Scholar]
  22. Tite J. P., Sloan A., Janeway C. A., Jr The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal. J Mol Cell Immunol. 1986;2(4):179–190. [PubMed] [Google Scholar]
  23. Weis R. M., Balakrishnan K., Smith B. A., McConnell H. M. Stimulation of fluorescence in a small contact region between rat basophil leukemia cells and planar lipid membrane targets by coherent evanescent radiation. J Biol Chem. 1982 Jun 10;257(11):6440–6445. [PubMed] [Google Scholar]

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