Cell-mediated PPD-specific cytotoxicity against human monocyte targets: evidence for restriction by class II HLA antigens

Human Purified Protein Derivative of tuberculin- (PPD-) specific cytotoxic cells have been detected in cultures of peripheral blood mononuclear cells stimulated for 6 days with PPD. These cytotoxic cells are demonstrated by their ability to lyse PPD-pulsed autologous monocyte target cells, but not unpulsed targets. In a series of checkerboard experiments each involving 3-5 randomly combined donors, effector cells from 35 donors have been tested in autologous and 130 allogeneic combinations. Analysis of results from the pooled allogeneic combinations reveals that HLA-B - and even more pronounced HLA-DR - antigen sharing correlates positively to high lysis. No effect of HLA-A antigen sharing is found. A more detailed analysis shows that the effect of HLA-B sharing may be fully accounted for by HLA-B-DR linkage disequilibrium. The results thus indicate that cell-mediated PPD specific cytotoxicity is HLA-restricted. Further, the correlation to HLA-DR sharing indicates that the restriction element in this system in all probability is a class II antigen.