Reactive T cells in the immune repertoire: self-restricted and allo-restricted helper T-cell clones to Epstein-Barr virus.

Helper T-cell clones were generated by stimulation with autologous or allogeneic lymphoblastoid B cells (B-LCL) transformed by the Epstein-Barr virus (EBV). Some of these T-cell clones were allo-reactive and others were specific to EBV-transformed B-LCL. Helper T-cell clones specific to EBV-transformed B-LCL were restricted either by class-I or by class-II HLA molecules of self. T-cell clones restricted by class-I HLA molecules were stained by OKT3 and OKT8 monoclonal antibodies (MAbs), whereas class-II-restricted clones stained with OKT3 and OKT4. Not all helper T-cell clones specific to EBV-transformed B-LCL were restricted to self: one clone restricted by allo-HLA antigen was established. This finding suggests that in humans, as in mice, some T cells in the T-cell repertoire can be allo-restricted. This allo restriction may represent cross-reactivity of T cells, whereby "self + X" equals "allo + Y." Activation of these cross-reacting T cells restricted by allogeneic HLA molecules during infectious mononucleosis will give a T-cell response which may appear unrestricted by self HLA molecules. This mechanism helps to explain, at least in part, the HLA unrestricted cytotoxicity to B-LCL observed in infectious mononucleosis.