title: Conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection.
abstract: 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 and class II structures and their maturation pathways have evolved to optimize antigen presentation to their respective T cells. A main focus of our laboratory is on efforts to understand molecular events in processing of antigen for presentation by MHC class II. The different stages of MHC class II-interactions with molecular chaperons involved in folding and traffic from the ER through the antigen-loading compartments, peptide exchange, and transport to the cell surface have been investigated. Through intense research on biophysical and biochemical properties of MHC class II molecules, we have learned that the conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection, and a determinant of the ability of MHC class II to participate in peptide association or dissociation and interaction with the peptide editor HLA-DM.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ssadegh@jhmi.edu
authors.forename: Scheherazade
authors.initials: S
authors.lastname: Sadegh-Nasseri
authors.forename: Sateesh
authors.initials: S
authors.lastname: Natarajan
authors.forename: Chih-Ling
authors.initials: CL
authors.lastname: Chou
authors.forename: Isamu Z
authors.initials: IZ
authors.lastname: Hartman
authors.forename: Kedar
authors.initials: K
authors.lastname: Narayan
authors.forename: AeRyon
authors.initials: A
authors.lastname: Kim
mesh_terms: D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology*; D006681:HLA-D Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D000939:Epitopes; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; D018832:Molecular Chaperones; D010455:Peptides