PRESENTATION OF ABUNDANT ENDOGENOUS CLASS-II DR-RESTRICTED ANTIGENS BY DM-NEGATIVE B-CELL LINES

Peptides derived from endogenous and exogenous antigens compete for bi nding and presentation via class II molecules. Studies with mutant B c ell lines defective in exogenous antigen presentation suggest that HLA -DM molecules facilitate the interaction of foreign peptides and class II molecules. In contrast, presentation of self antigens is not stric tly dependent upon HLA-DM, as demonstrated by the ability of these mut ant cells to activate T cells specific for endogenous antigens. Two di stinct classes of DM-negative cells, T2 cells generated by in vitro mu tagenesis and lines derived from bare lymphocyte syndrome (BLS) patien ts, were able to present epitopes derived from self proteins. Transfec tion of DM genes into the mutant cells enhanced the presentation of so me, but not all, endogenous antigens, suggesting that formation of sel ect endogenous peptide/class II complexes is not dependent upon DM. Th e efficiency of endogenous antigen presentation in the absence of DM w as also dependent on the mutant antigen-presenting cell studied, as th e TxB hybrid T2 presented greater amounts of self peptides compared to cells from BLS patients. Thus, additional genes, aside from DM, may r egulate the pathway for endogenous antigen presentation.