Cooperativity of hydrophobic anchor interactions: evidence for epitope selection by MHC class II as a folding process.

by MHC Class II as a Folding Process Interactions: Evidence for Epitope Selection Cooperativity of Hydrophobic Anchor

C-terminal anchoring of a peptide to class II MHC via the P10 residue is compatible with a peptide bulge.

The binding of antigenic peptide to class II MHC is mediated by hydrogen bonds between the MHC and the peptide, by salt bridges, and by hydrophobic interactions. The latter are confined to a number of deeper pockets within the peptide binding groove, and peptide side chains that interact with these pockets are referred to as anchor residues. T cell recognition involves solvent-accessible peptid...

Conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection.

T cells bearing alphabeta receptors recognize antigenic peptides bound to class I and class II glycoproteins encoded in the major histocompatibility complex (MHC). Cytotoxic and helper T cells respond respectively to peptide antigens derived from endogenous sources presented by MHC class I, and exogenous sources presented by MHC II, on antigen presenting cells. Differences in the MHC class I an...

HLA-DM Mediates Epitope Selection by a “Compare-Exchange” Mechanism when a Potential Peptide Pool Is Available

BACKGROUND HLA-DM (DM) mediates exchange of peptides bound to MHC class II (MHCII) during the epitope selection process. Although DM has been shown to have two activities, peptide release and MHC class II refolding, a clear characterization of the mechanism by which DM facilitates peptide exchange has remained elusive. METHODOLOGY/PRINCIPAL FINDINGS We have previously demonstrated that peptid...

Low-Affinity Major Histocompatibility Complex–Binding Peptides in Type 1 Diabetes

Type 1 diabetes is characterized by T-cell–mediated destruction of insulin-producing -cells. The strong association between autoimmune diabetes and certain susceptible major histocompatibility complex (MHC) class II alleles suggests that T-cell activation by self-peptides presented via these MHC class II alleles plays a critical role in the disorder’s pathogenesis. A diverse repertoire of T-cel...