A role for peptide in determining MHC class II structure

Publisher Website
Google Scholar
Abstract
T LYMPHOCYTES recognize antigen-derived peptides associated with major histocompatibility complex (MHC) class I or class II proteins1,2. Peptide is critical in class I heavy-chain folding and/or stable association with β2-microglobulin3–6. Although data exist suggesting a relationship between class II structure and peptide association7–9, no equivalent positive contribution of peptide to the folding state or stability of class II dimers has yet been demonstrated. We report here that most purified EαkEβk molecules leaving low pH in the absence of specific peptide lack a compact, stable dimeric structure. Brief exposure to the appropriate peptide just before and during neutralization promotes this specific conformation in proportion to stably bound peptide, indicating that peptide is important in determining class II MHC structure. Our results also indicate that efficient generation of long-lived peptide-class II complexes involves two stages: initial peptide binding in an acidic environment, which enhances the ability of class II to enter a conformation, from which stabilization upon neutralization results in high-affinity binding of previously associated peptide.