Selective inhibition of antigen‐induced “step one” in cytotoxic T lymphocytes by anti‐Lyt‐2 antibodies

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Abstract
Stimulation of [mouse] mixed lymphocyte cultures with UV-irradiated stimulator cells led to selective activation of Lyt-2+ cytotoxic T lymphocyte precursors (CTL-P) to acquire interleukin 2 (IL2) reactivity: no proliferative response, nor IL2 production was observed in these cultures; upon addition of performed IL2-conditioned media (IL2-CM), a vigorous proliferative response was observed; the IL2-dependent proliferation was reduced by .apprx. 90% after depletion of Lyt-2+ responder cells; and specific CTL were generated upon the initial triggering by UV-irradiated stimulators and IL2 expansion. This system provided suitable conditions for studying the role of Lyt-2 antigens in initial, antigen-specific induction of CTL-P, as well as their effector phase. Monoclonal anti-Lyt-2 antibodies inhibited antigen-specific acquisition of IL2 reactivity by CTL-P, which resulted in 85% reduction of the proliferative response mediated by IL2-CM. CTL-P which were induced by antigen to IL2 reactivity, before addition of anti-Lyt-2 antibodies were not affected in their IL2-dependent proliferation. Both the specific and lectin-dependent cytolytic activity of effector CTL generated by UV-irradiated stimulators and IL2-CM was blocked by addition of anti-Lyt-2 antibodies in the cytotoxicity assay. The implications of these findings for the role of Lyt-2 antigen in antigen recognition by T cells are discussed.