282 Epstein - Barr Virus - Specific Cytotoxic

Restriction of virus-specific cytotoxic T cell function by products of the major histocompatability complex (MHC), 1 a phenomenon first described in murine systems (1-3), has now been confirmed for the human T cell responses to antigens on cells infected by influenza (4, 5), Epstein-Barr (EB) (6, 7), and more recently, mumps (8), measles (9), and cytomegalo(10) 2 viruses. In each case the pattern of target cell iysis is consistent with a restriction through class I histocompatability antigens; moreover, monoclonal antibodies to these antigens have been shown to protect target cells both from influenza virusand EB virus-specific T cell-mediated cytotoxicity (11, 12). One important issue yet to be resolved concerns the relationship between those polymorphisms of HLA antigen structure that serve as restricting determinants for cytotoxic T cell function and those polymorphisms which have for some time been defined by serological techniques, i.e., by "HLA-type-specific" antisera obtained from multiparous women (13). Studies with influenza virus-specific cytotoxic T lymphocytes first indicated that the above relationship, although close, is not absolute. Thus HLA-A2restricted effector cells prepared from several different individuals all failed to recognize virus-infected target cells from a particular donor, M7, who was serologically typed as positive for HLA-A2 (14), and it was shown subsequently that M7's HLA-A2 antigen was distinct from the "common" A2 not only in terms of T cell restriction but also in its biochemical characteristics as revealed by isoelectric focusing (15, 16). Clearly human cytotoxic T cells specific for viruses other than influenza also have the potential ability to distinguish variation in class I HLA antigen structure. Indeed, in the long run, it will be important to determine whether cytotoxic T cells with different viral specificities all reveal the same pattern of HLA poly-