Conformational changes in mouse MHC class II proteins at acidic pH.
MHC class II molecules bind peptide antigens and present them to T cells. Recent evidence suggests that peptide--MHC class II interaction is regulated by pH. Both peptide binding to and dissociation from MHC class II molecules is enhanced at acidic pH. In this report we use circular dichroism to investigate the possibility that the modulation of peptide association with MHC class II molecules at acidic pH is associated with changes in MHC class II structure. Our results show that a change in the structure of the MHC class II protein A(d) occurs between pH 4 and 5, close to the pH optimum for peptide binding. More drastic changes in A(d) structure occur at lower pH levels, where peptide dissociation is enhanced. The structural changes at pH 4-5 are fully reversible upon neutralization, while changes at pH 3 are not. The pH stability of purified E(d) molecules is somewhat different, with changes observed only at pH less than 4. This may reflect a differential occupancy of the purified molecules with endogenous peptides.