The role of HLA antigens in the control of the cytotoxic T-cell response to Epstein-Barr virus: a family study.

Epstein-Barr (EB) virus-specific, HLA-restricted cytotoxic T-cell populations have been generated in vitro from each member of a family by cocultivating peripheral blood mononuclear cells with autologous EB virus-transformed B cells, the resulting effector cells being expanded as interleukin 2-dependent T-cell lines. The cytotoxicity of each of these effector populations was tested on a large panel of EB virus-transformed target cells of known HLA type, so that the particular HLA antigens which acted as restricting elements for each cytotoxic population could be identified. There was a consistent pattern within the family of preference for certain HLA class I antigens as restricting elements of the virus-specific T-cell response. Extensive functional analysis showed that, in addition to the virus-specific lysis, each effector population mediated a cross-reactive lysis against target cells prepared from certain HLA-mismatched individuals. This cross-reactivity appeared to be directed against HLA class I alloantigens and occurred irrespective of the EB virus genome status of the target cells. Effector T-cell lines derived from different family members but with virus-specific lysis predominantly restricted through the same HLA antigen showed similar patterns of concomitant allo-cross-reactivity. This suggests that antigenic mimicry of virally altered self by alloantigens is a genuine phenomenon which may be important in channelling the human cytotoxic T-cell response to a virus through preferred self-HLA determinants.