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. 1988 Dec 1;168(6):2077–2090. doi: 10.1084/jem.168.6.2077

Expression of a functional CD3-Ti antigen/MHC receptor in the absence of surface CD2. Analysis with clonal Jurkat cell mutants

PMCID: PMC2189161  PMID: 3264323

Abstract

To investigate the requirement for CD2 expression in activation of T lymphocytes via the CD3-Ti antigen/MHC receptor complex, we produced and characterized a series of CD2- Jurkat variants. These mutants lack detectable surface CD2 as determined by indirect immunofluorescence, immunoprecipitation analysis, and specific radiolabeled antibody binding assay, but nevertheless, expressed normal numbers of CD3-Ti receptors. As expected, the combination of anti-CD2 antibodies, termed anti-T112 and anti-T113, which are mitogenic for resting T lymphocytes, failed to stimulate activation of these variants. In contrast, triggering of their CD3-Ti components resulted in the normal set of T lymphocyte-associated activation events, including phosphoinositide turnover, elevation in intracellular free calcium, early gene-induction events, and IL-2 production. Assuming that the Jurkat cell line is representative of normal cycling human T lymphocytes, we conclude that the presence of the CD2 molecule on the plasma membrane is not in itself a requirement for an operational CD3-Ti-alpha/beta receptor.

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Selected References

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  1. Alcover A., Alberini C., Acuto O., Clayton L. K., Transy C., Spagnoli G. C., Moingeon P., Lopez P., Reinherz E. L. Interdependence of CD3-Ti and CD2 activation pathways in human T lymphocytes. EMBO J. 1988 Jul;7(7):1973–1977. doi: 10.1002/j.1460-2075.1988.tb03035.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alcover A., Weiss M. J., Daley J. F., Reinherz E. L. The T11 glycoprotein is functionally linked to a calcium channel in precursor and mature T-lineage cells. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2614–2618. doi: 10.1073/pnas.83.8.2614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  4. Bierer B. E., Barbosa J., Herrmann S., Burakoff S. J. Interaction of CD2 with its ligand, LFA-3, in human T cell proliferation. J Immunol. 1988 May 15;140(10):3358–3363. [PubMed] [Google Scholar]
  5. Breitmeyer J. B., Daley J. F., Levine H. B., Schlossman S. F. The T11 (CD2) molecule is functionally linked to the T3/Ti T cell receptor in the majority of T cells. J Immunol. 1987 Nov 1;139(9):2899–2905. [PubMed] [Google Scholar]
  6. Denning S. M., Tuck D. T., Singer K. H., Haynes B. F. Human thymic epithelial cells function as accessory cells for autologous mature thymocyte activation. J Immunol. 1987 Feb 1;138(3):680–686. [PubMed] [Google Scholar]
  7. Denning S. M., Tuck D. T., Vollger L. W., Springer T. A., Singer K. H., Haynes B. F. Monoclonal antibodies to CD2 and lymphocyte function-associated antigen 3 inhibit human thymic epithelial cell-dependent mature thymocyte activation. J Immunol. 1987 Oct 15;139(8):2573–2578. [PubMed] [Google Scholar]
  8. Dustin M. L., Sanders M. E., Shaw S., Springer T. A. Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. J Exp Med. 1987 Mar 1;165(3):677–692. doi: 10.1084/jem.165.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Faure F., Jitsukawa S., Meuer S., Bohuon C., Triebel F., Hercend T. Identification of a CD2- CD3+ T cell receptor-gamma+ peripheral blood lymphocyte subpopulation. J Immunol. 1988 Apr 1;140(7):2128–2132. [PubMed] [Google Scholar]
  10. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  11. Holter W., Majdic O., Stockinger H., Howard B. H., Knapp W. Regulation of the CD2 alternate pathway of T cell activation by CD3. Evidence for heterologous desensitization. J Immunol. 1988 Feb 15;140(4):1043–1046. [PubMed] [Google Scholar]
  12. Hünig T., Tiefenthaler G., Meyer zum Büschenfelde K. H., Meuer S. C. Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand. Nature. 1987 Mar 19;326(6110):298–301. doi: 10.1038/326298a0. [DOI] [PubMed] [Google Scholar]
  13. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kuno M., Gardner P. Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes. Nature. 1987 Mar 19;326(6110):301–304. doi: 10.1038/326301a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Meuer S. C., Hodgdon J. C., Hussey R. E., Protentis J. P., Schlossman S. F., Reinherz E. L. Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. J Exp Med. 1983 Sep 1;158(3):988–993. doi: 10.1084/jem.158.3.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pantaleo G., Olive D., Poggi A., Kozumbo W. J., Moretta L., Moretta A. Transmembrane signalling via the T11-dependent pathway of human T cell activation. Evidence for the involvement of 1,2-diacylglycerol and inositol phosphates. Eur J Immunol. 1987 Jan;17(1):55–60. doi: 10.1002/eji.1830170110. [DOI] [PubMed] [Google Scholar]
  19. Pantaleo G., Olive D., Poggi A., Pozzan T., Moretta L., Moretta A. Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation. J Exp Med. 1987 Aug 1;166(2):619–624. doi: 10.1084/jem.166.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sayre P. H., Chang H. C., Hussey R. E., Brown N. R., Richardson N. E., Spagnoli G., Clayton L. K., Reinherz E. L. Molecular cloning and expression of T11 cDNAs reveal a receptor-like structure on human T lymphocytes. Proc Natl Acad Sci U S A. 1987 May;84(9):2941–2945. doi: 10.1073/pnas.84.9.2941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Truneh A., Albert F., Golstein P., Schmitt-Verhulst A. M. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Nature. 1985 Jan 24;313(6000):318–320. doi: 10.1038/313318a0. [DOI] [PubMed] [Google Scholar]
  22. Yang S. Y., Chouaib S., Dupont B. A common pathway for T lymphocyte activation involving both the CD3-Ti complex and CD2 sheep erythrocyte receptor determinants. J Immunol. 1986 Aug 15;137(4):1097–1100. [PubMed] [Google Scholar]
  23. Yssel H., Aubry J. P., de Waal Malefijt R., de Vries J. E., Spits H. Regulation by anti-CD2 monoclonal antibody of the activation of a human T cell clone induced by anti-CD3 or anti-T cell receptor antibodies. J Immunol. 1987 Nov 1;139(9):2850–2855. [PubMed] [Google Scholar]

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