The cellular requirements for the generation of cytotoxicity in mixed lymphocyte reaction (MLR) across an H-2K mutant difference were analyzed. Treatment of C57BL/6 lymphocytes with either anti-Lyt-1 or anti-Lyt-2 serum and complement strongly reduced their capacity to mount a cytotoxic response against the B6.C-H-2ba mutant. Almost complete reconstitution of the cytotoxic response occurred when a mixture of anti-Lyt-1 and anti-Lyt-2-treated cells was allowed to respond. Once cytotoxicity was generated, only anti-Lyt-2 serum affected it. It is concluded that in the cytotoxic response to the ba mutant, Lyt-1 helper cells collaborate with Lyt-2,3 killer cell precursors in the generation of Lyt-2,3 killer cells. Lyt-1,2,3 cells play, if any, a minor role in the generation of cytotoxicity. By comparison, the capacity to generate killer cells in MLR against an H-2K + IA difference was only affected by anti-Lyt-2 and not by anti-Lyt-1 serum, indicating that this response is relatively independent of help by Lyt-1 cells under the conditions tested.

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