Fine specificity of cytotoxic T lymphocytes directed against H-2Ld.

The fine specificity of cytotoxic T lymphocytes (CTL) directed against H-2Ld was analyzed by studying the lytic activity of BALB/c H-2dm2 (H-2Ld loss mutant) anti-BALB/c-H-2d CTL, generated in secondary mixed lymphocyte culture (MLC) against a panel of target cells of different H-2 haplotypes. Target cells of all H-2 haplotypes tested, except that of the MLC responder, were lysed by anti-Ld CTL, although to a widely varying extent. The genes coding for antigens detected by anti-Ld CTL were mapped to distinct regions in the H-2d, H-2dm1, H-2q, H-2k, and H-2b haplotypes. The sequence of lysis intensity against the various H-2 haplotypes and the H-2 regions involved were as follows: Ld, DqLq, Ddm1 Ldm1, Kk, DbLb, r, p, f, s, C3h.OH (KdDkLk), strong lysis occurring against Ld and weak lysis against H-2s and C3H.OH. By monolayer adsorption and cold target inhibition experiments, it was shown that anti-Ld CTL contained a CTL subset directed against a private Ld specificity, hitherto undetected by anti-Ld antibodies. This subset a CTL was separate from the CTL subsets reacting against H-2q and against the mutant haplotype H-2dm1. The reactions against the latter two haplotypes were also mediated by separate CTL subsets. It is concluded that the Ld molecule, to a varying extent, shares target antigens for CTL and K- and/or D-end H-2 molecules of all haplotypes tested. These antigens are detected by multiple subsets of anti-Ld CTL. One CTL subset is directed against a target structure unique for Ld (Ld private specificity).