Peptide ligand structure influences the exchange of beta(2)-microglobulin by cell surface K-b

We have studied the interactions which occur between the peptide ligand and beta(2)-microglobulin (beta(2)m) components of the class I MHC complex by analysing the process of beta(2)m exchange. We have previously shown that t he rate of beta(2)m exchange on a cell-surface class I MHC complex varies w ith the peptide ligand to which it is bound. It remains unclear, however, w hether the ability of peptide ligand to alter beta(2)m/heavy-chain associat ion is related to peptide affinity, peptide structure, or both. In this art icle, we examine the effects of variations in peptide ligand structure on t he rate of beta(2)m exchange by cell surface K-b complexes. Using a panel o f alanine substituted variants of the MCMV peptide (YPHFMPTNL), we show tha t single amino acid changes in peptide sequence can have dramatic effects o n the rates of beta(2)m exchange. The observed changes in beta(2)m exchange rates are directly due to modification of the peptide ligand structure as they do not reflect changes in peptide affinity. These findings suggest tha t peptide ligand structure can induce conformational changes in the K-b hea vy chain which alter the rates of cell surface beta(2)m exchange, and provi de further evidence For peptide-dependent fluidity of the class I heavy cha in. (C) 1998 Elsevier Science Ltd. All rights reserved.