EPSTEIN-BARR-VIRUS INFECTION ABROGATES THE STIMULATORY CAPACITY OF B-CELLS TO A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-RESTRICTED PROLIFERATIVE T-CELL CLONE

After BMT, donor T tells are activated which can display GvHD as well as GvL activities. In order to study this GvL-specific T-cell response in vitro, proliferative T-cell clones from post-BMT PBMCs were genera ted by stimulation with a patient's leukemic cells. One CD4(+) T-cell clone (designated M-33) displayed strong proliferative activity agains t the patient's leukemic cells but not against the patient's EBV-LCLs. The induction of proliferation, however, appeared not to be leukemia specific. Detailed analysis of the reactivity patterns revealed that T -cell clone M-33 recognizes an as yet unknown nonpolymorphic determina nt in the context of self HLA-DRw52, presented by all but one type of APC. T-cell clone M-33 proliferated upon stimulation by PB-MCs, freshl y isolated B cells, monocytes, dendritic cells, leukemic B cells, and nonleukemic B-cell blasts; solely in vitro EBV-transformed B cells and in vivo EBV-infected B cells failed to induce proliferation of T-cell clone M-33. Neither surface expression of MHC or accessory molecules on the EBV cells nor suppression caused by the EBV-infected cells coul d explain their failure to stimulate T-cell clone M-33. We therefore h ypothesize that the absence of the stimulatory capacity once the B cel ls are virally infected could be the result of competition for MHC cla ss II binding of the Epstein-Barr viral peptides, thus affecting the p ostulated DRw52-restricted peptide for recognition by T-cell clone M-3 3.