Bacterial proteins that mediate the association of a defined subset of T cell receptor:CD4 complexes with class II MHC.
We have examined the responses of cloned T cell lines and of normal T cells to staphylococcal enterotoxins A, B, and C1 (SEA, SEB, and SEC1). SEA, SEB, and SEC1 are all very potent mitogens for T cells in the presence of Ia+ APC. The minimal activating dose of all these SE varies from 1 to 100 ng/ml. As determined by mAb blocking of the responses of both normal T cells and cloned T cell lines, SEA required either the I-A or the I-E molecule on APC for stimulating T cells, whereas SEB required the I-E molecule predominantly over I-A molecule. The TCR:CD4 complex is also involved in the response to SE. The responses to SEB and SEC1 were inhibited by anti-V beta 8 antibody F23.1, whereas the response to SEA and to PHA was not affected by this antibody. Anti-CD4 effectively inhibited responses to all SE but not to PHA. The involvement of the TCR was also confirmed by flow microfluorimetry analysis of T cell blasts responding to SE and the responses of a panel of cloned T cell lines, both of which showed that V beta 8+ T cells preferentially responded to SEB, whereas V beta 8+ T cells failed to respond to SEA. By using fixed APC, it could be shown that processing is not required for the presentation of SE. Furthermore, pulsing experiments showed that SEB can bind to relevant sites on either B cells or T cells, whereas with conventional Ag only prepulsing of the APC has worked. In one case, SEB activates a cloned T cell line in the absence of APC, and this same clone also responds directly to anti-V beta 8 antibody. Thus, SEB appears to bring together V beta 8-expressing TCR with the I-E molecule, whereas SEA apparently has the same effect on TCR expressing different V beta with either the I-A or the I-E molecule, probably depending upon which TCR is bound. The close resemblance between T cell responses to SE and those to mixed-lymphocyte stimulating (Mls) locus suggests to us that a novel SE-like protein that binds both to class II MHC molecules on the APC surface and to V beta gene products on TCR could be the product of the Mls locus.
Yagi
J
J
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.
Baron
J
J
Buxser
S
S
Janeway
C A
CA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D000954:Antigens, Surface / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000502:physiology*; D002999:Clone Cells; D004768:Enterotoxins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D016747:Minor Lymphocyte Stimulatory Antigens; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013211:Staphylococcus aureus; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D000954:Antigens, Surface; D015704:CD4 Antigens; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta