Up-regulation of the MHC class II molecules on B cells by peptide ligands.

MHC class I and class II molecules present peptide Ag to T lymphocytes. Peptides are critical in class I heavy chain folding and/or stable association with beta 2m. A recent study suggests the role of peptide Ag binding for MHC class II alpha- and beta-chain heterodimers to enter into a compact state and allow their transport to the cell surface. We have investigated the effect of peptide ligands on the expression of MHC class II I-A(d) molecules on the B cell hybridoma, TA3. These cells, when cultured in vitro, gradually lost the surface expression of I-A(d) molecules. Incubation with peptides, having high affinity for binding to intact I-A(d) molecules, significantly increased the surface expression of I-A(d) in less than 24 h. The ability of peptides to induce increased expression of I-A(d) correlated with the affinity of peptide to intact I-A(d), and an I-Ak-restricted peptide did not have an effect on I-A(d) expression. The effect could be reversed after the removal of the peptide Ag. Based on our studies with inhibitors of protein synthesis and intracellular transport, the mechanism for up-regulation of I-A(d) expression by peptides seems to involve intracellular pathway but appears not to require new protein synthesis or transport from ER. Our results suggest that the decrease in surface expression of I-A(d) on TA3 cells may result from their failure to generate or to be saturated with naturally processed peptide ligands. Thus peptide ligands are evidently important in regulating surface expression of MHC class II molecules and their recognition by T lymphocytes.