Article

Immunologic Research

, Volume 47, Issue 1, pp 56-64

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

  • Scheherazade Sadegh-NasseriAffiliated withDepartment of Pathology, Johns Hopkins University School of Medicine Email author 
  • , Sateesh NatarajanAffiliated withDepartment of Pathology, Johns Hopkins University School of MedicineDendreon
  • , Chih-Ling ChouAffiliated withDepartment of Pathology, Johns Hopkins University School of MedicineProgram in Neuroscience, The University of Arizona, College of Pharmacy
  • , Isamu Z. HartmanAffiliated withDepartment of Pathology, Johns Hopkins University School of MedicineDepartment of Molecular Genetics, University of Texas Southwestern Medical Center
  • , Kedar NarayanAffiliated withDepartment of Pathology, Johns Hopkins University School of MedicineLaboratory of Cell Biology, NCI, NIH
  • , AeRyon KimAffiliated withDepartment of Pathology, Johns Hopkins University School of Medicine

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Abstract

T cells bearing αβ 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.

Keywords

MHC class II Kinetics Conformational heterogeneity Immunodominance H-bonds Peptide-receptive conformation