The role of CD2/LFA-3 interaction in antigen- and mitogen-induced activation of human T cells.
Binding of LFA-3 to the T cell surface receptor CD2 promotes intercellular adhesion and is costimulatory with anti-CD2 mAbs in 'alternative pathway' activation of T cells. Since all AC-dependent systems of T cell activation are inhibited by anti-LFA-3 mAb, it was asked whether in mitogen- and antigen-induced activation of human T cells, the function of CD2/LFA-3 interaction involves signalling beyond its function in promoting intercellular adhesion. In order to selectively block and reconstitute CD2/LFA-3 interaction while leaving other AC functions available, the response of unseparated PBMC to various T cell mitogens and to allogeneic cells was blocked by a newly developed mAb (G26) to human LFA-3. Addition of purified T11TS, the sheep form of LFA-3 that binds to human CD2 but is not recognized by mAb G26, restored the T cell response to PHA-P but not to ConA, surface aldehydes, anti-CD3 mAb, or allogeneic cells. In addition, purified resting human T cells which were unresponsive to stimulation by lectins or anti-CD3 mAbs were activated by PHA-P in the presence of purified T11TS, demonstrating that provision of LFA-3 is a sufficient accessory cell function in the activation of human T cells by this mitogen. Again, the responses to ConA, cell surface aldehydes, or soluble anti-CD3 mAb were not restored by T11TS. T cell activation by PHA-P, but not by the other polyclonal T-cell activators studied thus seems to be mechanistically similar to 'alternative pathway' activation induced by anti-CD2 mAb in that the costimulatory effect of LFA-3 is independent of its prescence on an accessory cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Tiefenthaler
G
G
Genzentrum der Ludwig Maximilians Universität München, Martinsried, Federal Republic of Germany.
Hünig
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D001667:Binding, Competitive; D018801:CD2 Antigens; D018968:CD58 Antigens; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D008934:Mitogens / Q000494:pharmacology; D011971:Receptors, Immunologic; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D008934:Mitogens; D011971:Receptors, Immunologic