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Fine specificity of cytotoxic T lymphocytes directed againstH-2L d
Authors:C J M Melief  L P de Waal  M Y van der Meulen  P Iványi  R W Melvold
Institution:(1) Department of Tumor Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands;(2) Department of Immunohematology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands;(3) Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands;(4) Section of Medical Oncology, Departments of Medicine and Microbiology-Immunology, Northwestern University, 303 E. Chigaco Avenue, 60611 Chicago, Illinois
Abstract:The fine specificity of cytotoxic T lymphocytes (CTL) directed againstH-2L d was analyzed by studying the lytic activity of BALB/cH- 2dm2 (H-2L d loss mutant) anti-BALB/c-H-2 d CTL, generated in secondary mixed lymphocyte culture (MLC) against a panel of target cells of differentH-2 haplotypes. Target cells of allH-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-L d CTL were mapped to distinct regions in theH-2 d ,H- 2dm1,H-2 q ,H-2 k , andH-2 b haplotypes. The sequence of lysis intensity against the variousH-2 haplotypes and theH-2 regions involved were as follows:L d ,D q L q ,D dm1 Ldm1,K k ,D b L b ,r, p, f, s, C3H.OH (K d D k L k ), strong lysis occurring againstL d and weak lysis againstH-2 s and C3H.OH.By monolayer adsorption and cold target inhibition experiments, it was shown that anti-L d CTL contained a CTL subset directed against a private Ld specificity, hitherto undetected by anti-L d antibodies. This subset of CTL was separate from the CTL subsets reacting againstH-2 q and against the mutant haplotypeH- 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 with K- and/or D-end H-2 molecules of all haplotypes tested. These antigens are detected by multiple subsets of anti-L d CTL. One CTL subset is directed against a target structure unique forL d (Ld private specificity).
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