title: Conformational isomers of a peptide-class II major histocompatibility complex.
abstract: The relative plasticity of peptide binding to class II major histocompatibility complex (MHC) molecules permits formation of multiple conformational isomers by the same peptide and MHC molecule; such conformers are specifically recognized by distinct subsets of T cells. Here, we review current knowledge and recent advances in our understanding of peptide-class II MHC conformational isomerism and the mechanisms that generate distinct MHC-peptide conformers. We focus on our studies of two T-cell subsets, type A and B, which recognize distinct conformers of the dominant epitope of hen egg white lysozyme presented by I-A(k). These conformers form via different pathways and in distinct intracellular vesicles: the type A conformer forms in late endosomes upon processing of native protein, while the more flexible type B conformer forms in early endosomes and at the cell surface. In this process, H2-DM acts as a conformational editor, eliminating the type B conformer in late endosomes. Type B T cells constitute a significant component of the naïve T-cell repertoire; furthermore, self-reactive type B T cells escape negative selection and are present in abundance in the periphery. Ongoing studies should elucidate the role of type B T cells in immunity to pathogens and in autoimmune pathology.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Lovitch
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007536:Isomerism; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D009113:Muramidase / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D010455:Peptides; C421864:hen egg lysozyme; D009113:Muramidase