Analysis of T-T lymphocytes and T-accessory cell interactions using cloned T cells: MHC I restricted cloned T cells activate MHC II restricted T helper cells.
We evaluated the role of molecules of the major histocompatibility complex (MHC) involved in the cellular interactions of two T-cell clones by testing the effect of monoclonal antibodies on the responses of the clones in vitro. The two T-cell clones used in the study are specific for minor histocompatibility antigens and restricted to the H-2Kk. In the absence of exogenous IL-2 the clones require the presence of Ia+, Thy-1- accessory cells and of Thy-1+, Lyt-1+2- cells in the irradiated spleen cell suspension used as stimulator. It is also necessary that both the accessory cells and the T cells in the stimulator cell populations are recognized specifically by the clones. Monoclonal antibodies specific for the H-2K product inhibited the lytic effector function of the cytolytic clone. These antibodies when added to cultures of stimulator cells and clones inhibited also the proliferation of this clone and of a nonlytic clone. When antigen recognition was measured by the increase in sensitivity of the clones to IL-2 while confronted with uv-irradiated stimulator cells, both clones were blocked efficiently by anti-H-2K antibodies. Thus, these results suggest that the interaction of monoclonal antibodies with the restricting H-2K molecule is sufficient to block the recognition signal, a prerequisite for proliferation. In contrast, monoclonal antibodies specific for A alpha A beta and/or E alpha E beta had no effect on cytolysis or on restricted recognition. However, they inhibited the proliferative responses as efficiently as the H-2K specific antibodies. Inhibition by class II-specific antibodies was not abolished when stimulator cell populations were depleted of Lyt-2+ cells. The blocking effect, however, was reversed by the addition of IL-2. No inhibition was obtained with antibody specific for E alpha E beta when B10.A(4R) spleen cells, which do not express E alpha E beta, or when B10.A(4R) accessory cells, which were reconstituted with (BALB/c X B10.A(4R] F1 T cells, were used as stimulators. Stimulator cells heterozygous for H-2 could be inhibited by antibodies to the parental haplotype not encoded in the clones (H-2Kd). These and previous results suggest that H-2K-restricted minor histocompatibility antigen-specific recognition transmits an activating signal to the clones and to the stimulator cells. The clones probably are induced to express more IL-2 receptors. The stimulator T cells seem to interact through A alpha A beta and E alpha E beta molecules with syngeneic accessory cells.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D002450:Cell Communication; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000954:Antigens, Surface; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D018800:Thy-1 Antigens