The role of the trimolecular complex (alpha beta TCR-MHC+peptide) in the pathogenesis of systemic sclerosis.
Systemic sclerosis is an intricate disease process whose most unique and specific parameter indicative of autoimmunity is the presence of autoantibodies directed against certain nuclear antigens. The relationship between this particular humoral immune response and the genesis of a fibrotic tissue response in the skin as well as internal organs is not yet well understood. The prominence of CD4 T-cell infiltration during early phases of disease suggest that activation pathways may be initiated which subsequently result in phenotypic changes of a variety of mesenchymal cells, especially endothelial cells and fibroblasts. Taken in concert with the association of susceptibility with certain MHC class II molecules, the conventional presenters of exogenous peptide to T cells of the CD4 lineage, the notion of a central critical immune recognition event underlying the development of systemic sclerosis gains increasing likelihood. In addition to the still incompletely understood paracrine pathways between immune response and fibrosis, there is a nearly complete void of knowledge concerning what peptide is recognized by the T-cell and the structure of the alpha beta TCR involved in this recognition. Determining the role of the alpha beta TCR in the activation of the T-cell population in terms of identifying structural features which are critical participants in this process and the functional derangement leading to the characteristic pattern of self recognition will certainly enhance our understanding of the pathogenesis of systemic sclerosis.
Dwyer
E
E
Department of Pediatrics, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
Winchester
R
R
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000209:etiology*; D012641:Selection, Genetic; D013601:T-Lymphocytes / Q000276:immunology
D001324:Autoantigens; D010455:Peptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta