title: Structural Insights Into HLA-DM Mediated MHC II Peptide Exchange.
abstract: Antigen presentation by class II MHC proteins (MHC-II) is a critical component of the adaptive immune response to foreign pathogens. Our understanding of how antigens are presented has been greatly enhanced by crystallographic studies of MHC-II-peptide complexes, which have shown a canonical extended conformation of peptide antigens within the peptide-binding domain of MHC-II. However, a detailed understanding of the peptide loading process, which is mediated by the accessory molecule HLA-DM (DM), remains unresolved. MHC-II proteins appear to undergo conformational changes during the peptide loading/exchange process that have not been clearly described in a structural context. In the absence of a crystal structure for the DM-MHC-II complex, mutational studies have provided a low resolution understanding as to how these molecules interact. This review will focus on structural and biochemical studies of the MHC-II-peptide interaction, and on studies of the DM-MHC-II interaction, with an emphasis on identifying structural features important for the mechanism of DM mediated peptide catalysis.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology and Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655 USA.
authors.forename: Corrie A
authors.initials: CA
authors.lastname: Painter
authors.affiliation: Department of Biochemistry and Molecular Pharmacology and Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655 USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Stern
keywords: Antigen Presentation; H2-M; HLA-DP; HLA-DQ; HLA-DR; I-A; I-E; Immune Response; MHC protein