[Molecular mimicry and mechanisms of autoantibody production].
Molecular mimicry is defined as similar structures shared by products of dissimilar genes. This review article discusses a possible role of molecular mimicry in the production of autoantibodies. Antibodies reactive with products of bacterial and viral genes sometime cross-react with normal cellular proteins. Sera from patients with systemic autoimmune diseases show crossreactivity with some bacterial and/or viral gene products at a significant frequency. Identification of the structures of antigenic epitopes recognized by disease-associated autoantibodies by expression cloning of autoantigen molecules and gene fragment expression revealed the amino acid residues that are shared by autoantibody-defined epitopes and microbial proteins. The presence of amino acid sequences shared between microbial proteins and autoantigens and the detection of antibodies in patients' sera that bind to the crossreactive epitopes suggest that immune responses to bacterial and viral infections may initiate the production of autoantibodies. Receptor-mediated phagocytosis of autoantigen molecules by crossreactive B cells and subsequent antigen presentation to helper T cells may facilitate the production of autoantibodies reactive with separate epitopes, if the autoantigen complex contains multiple B-cell epitopes and a shared T helper cell epitope. Analyses of the fine specificity of T helper cell epitopes on Friend murine leukemia virus env gene products revealed unexpected heterogeneity and redundancy of T cell responses even to a single epitope. This heterogeneity in T cell responses might play a role in the activation of self-reactive T helper cells through molecular mimicry.
Miyazawa
M
M
Department of Immunology, Kinki University School of Medicine.
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes; D006801:Humans; D018716:Molecular Mimicry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes