Epstein-Barr virus-specific cytotoxic T lymphocytes as probes of HLA polymorphism. Heterogeneity of T cell-restricting determinants associated with the serologically defined HLA-A2 antigen.

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Abstract
Epstein-Barr (EB) virus-specific effector T cell lines were established from 9 virus-immune donors positive for the serologically defined HLA-A2 antigen; of these, 4 lines contained a demonstrable A2-restricted cytotoxic component. When these 4 effector populations were each tested on the same panel of EB virus transformed lines from 20 HLA-A2-positive individuals, 16 of the target cell lines were consistently killed at levels > 25% of the relevant autologous cell lysis. Cytotoxicity appeared to be mediated through a restricting determinant associated with the common A2 antigen that these lines shared; the lysis could be specifically blocked by high concentrations of an HLA-A2-specific monoclonal antibody. Of 20 target cell lines, 4 were not killed by HLA-A2-restricted effector cells, even though they did express the serologically defined A2 antigen and were found in other tests to be susceptible to EB virus-specific cytolysis restricted through other HLA-A or -B antigens on their surface. Evidently, EB virus-specific cytotoxic T cells can distinguish between serologically identical HLA-A2 molecules via the heterogeneity of their T cell-restricting determinants. Data from one of the effector cell populations further suggested that a serologically defined cross-reaction between the otherwise distinct HLA-A2 and -Bw57 antigens might also be reflected in a cross-reactivity of T cell-restricting determinants.