EVIDENCE FOR THE INVOLVEMENT OF HLA-DR ANTIGENS IN RESTRICTED CYTO-TOXICITY BY FETAL CALF SERUM-SPECIFIC HUMAN T-CELLS

Fetal calf serum (FCS) generated at least 2 distinct populations of human cytotoxic cells in vitro. One population expressed natural killer (NK) cell-like activity and lysed human leukemia K562 and HSB-2 targets more effectively than autologous or allogeneic lymphoblastoid cell lines (LCL). The other population contained FCS-specific cytotoxic T cells which preferentially lysed the autologous LCL and showed minimal lysis of K562. E[erythrocyte]-rosette separation and cold target competition experiments clearly established that NK cells were not involved in the self-reactive lysis. The lytic activity of the E-rosetted T cells was reduced by up to 95% when autologous target cells were grown in human AB serum rather than FCS, showing that FCS-associated determinants on targets were essential in the cytolytic phase. Autologous LCL grown in FCS were also considerably stronger competitors than human serum-grown LCL. The consistent self-preferred lysis suggested that HLA antigen-related restriction was involved, but the patterns of lysis did not implicate HLA-A or B antigens, and monoclonal antibody (W6/32) to an A, B and C monomorphic determinant failed to block FCS-specific lysis. Monoclonal antibody (DA.2) to a monomorphic determinant of DR effectively blocked FCS-specific lysis. Cytotoxicity tests with a small panel of DR-typed donors indicated that strong cross-reactions were invariably associated with sharing of DR antigens, particularly DR2, and to a lesser but significant extent DR7. Although DR antigen sharing did not always result in lysis of allogeneic targets, FCS-specific T-cell cytotoxicity in humans is apparently restricted by products encoded by or associated with the DR genes.