Cross-reactivity of self-HLA-restricted Epstein-Barr virus-specific cytotoxic T lymphocytes for allo-HLA determinants.
Epstein-Barr (EB) virus-specific cytotoxic T cells, prepared from virus-immune donors by reactivation in vitro and maintained thereafter as IL-2-dependent T cell lines, have been tested against large panels of EB virus-transformed lymphoblastoid cell lines of known HLA type. Whilst the pattern of lysis of the majority of targets was always consistent with HLA-A and HLA-B antigen restriction of effector function, in several cases it was noticed that certain HLA-mismatched targets were also reproducibly lysed. When this "anomalous" lysis was investigated in detail, it was found to be directed against allodeterminants on class I HLA antigens; thus, mitogen-stimulated as well as EB virus-transformed lymphoblasts from the relevant target cell donors were sensitive to the killing, and in each case the lysis could be specifically blocked by monoclonal antibodies to class I HLA antigens. In one example the target for this alloreactive lysis could be identified as a single serologically defined antigen, HLA-Bw57, while in another example lysis was directed against a "public" epitope common to HLA-Bw35, -Bw62, and a subset of -B12 antigens. Both cold target inhibition experiments and limiting dilution analysis strongly suggested that this alloreactive lysis was being mediated by the same effector T cells that recognize EB viral antigens in the context of self-HLA. This is the first demonstration in man that alloreactive responses can be derived from within the antigen-specific, self MHC-restricted T cell repertoire.
D000911:Antibodies, Monoclonal; D002460:Cell Line; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006680:HLA Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006680:HLA Antigens; D007519:Isoantigens