Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein.
Structural similarity between viral T cell epitopes and self-peptides could lead to the induction of an autoaggressive T cell response. Based on the structural requirements for both MHC class II binding and TCR recognition of an immunodominant myelin basic protein (MBP) peptide, criteria for a data base search were developed in which the degeneracy of amino acid side chains required for MHC class II binding and the conservation of those required for T cell activation were considered. A panel of 129 peptides that matched the molecular mimicry motif was tested on seven MBP-specific T cell clones from multiple sclerosis patients. Seven viral and one bacterial peptide efficiently activated three of these clones. Only one peptide could have been identified as a molecular mimic by sequence alignment. The observation that a single T cell receptor can recognize quite distinct but structurally related peptides from multiple pathogens has important implications for understanding the pathogenesis of autoimmunity.
Wucherpfennig
K W
KW
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138.
Strominger
J L
JL
D000595:Amino Acid Sequence; D000940:Antigenic Variation; D015551:Autoimmunity / Q000276:immunology*; D002461:Cell Line, Transformed; D016208:Databases, Factual; D006681:HLA-D Antigens / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry; D008213:Lymphocyte Activation; D018448:Models, Immunological; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D006681:HLA-D Antigens; D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins