Characterization of dual-reactive H-2Kb-restricted anti-vesicular stomatitus virus and alloreactive cytotoxic T cells.
Cross-reactive recognition of alloantigen by "self + X"-reactive cytotoxic T lymphocytes (CTL) has been documented in a variety of systems. It has been shown previously that the H-2Kb-restricted CTL response of C57BL/6 (B6) mice to vesicular stomatitis virus (VSV) infection is partially cross-reactive on uninfected target cells expressing the H-2Kbm8 mutation. In this report, we describe the isolation and detailed characterization of such dual-reactive CTL. By employing EL4 tumor lines transfected with genes encoding various VSV proteins, we demonstrated that the majority of dual-reactive CTL recognize the internal N protein of VSV and are also reactive against uninfected bm8 targets. Although the response of normal B6 mice to bm8 stimulators shows no measurable cross-reactivity on VSV-infected targets, the response of VSV-primed B6 mice to bm8 stimulation is almost entirely cross-reactive, lysing VSV-B6 targets and uninfected bm8 targets roughly equally. Furthermore, about 70% of CTL clones isolated from such mice by bm8 stimulation are dual-reactive with respect to effector function. Analysis at the population and clonal levels with cold target competition and antibody blocking suggests that the bulk of dual-reactive CTL have a higher avidity for VSV-B6 targets than for bm8 targets. The extreme case of this is illustrated by a fraction of CTL clones, isolated and maintained on bm8 stimulators, which lyse VSV-B6 targets but do not lyse bm8 targets. One such CTL clone is shown to be specific for the bm8 antigen in proliferation assays. These results demonstrate that: the specificity of an alloreactive CTL response may be dramatically altered by previous antigenic encounters; and dual-reactive CTL display a significant difference in affinity of the CTL receptor-determinant interaction, depending on the target which is recognized.
D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D009439:Neuraminidase / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000954:Antigens, Surface; D006183:H-2 Antigens; D007519:Isoantigens; D016169:Lymphocyte Function-Associated Antigen-1; D009439:Neuraminidase