Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein

Cell. 1995 Mar 10;80(5):695-705. doi: 10.1016/0092-8674(95)90348-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigenic Variation
  • Autoimmunity / immunology*
  • Cell Line, Transformed
  • Databases, Factual
  • HLA-D Antigens / metabolism
  • Humans
  • Immunodominant Epitopes / chemistry
  • Lymphocyte Activation*
  • Models, Immunological
  • Molecular Mimicry / immunology*
  • Molecular Sequence Data
  • Multiple Sclerosis / immunology
  • Myelin Basic Protein / immunology*
  • Peptide Fragments / chemistry
  • Peptides / chemistry
  • Peptides / immunology
  • Peptides / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology*
  • Viral Proteins / chemistry
  • Viral Proteins / immunology*
  • Viral Proteins / metabolism


  • HLA-D Antigens
  • Immunodominant Epitopes
  • Myelin Basic Protein
  • Peptide Fragments
  • Peptides
  • Receptors, Antigen, T-Cell
  • Viral Proteins