POSITIVE SELECTION IN AUTOIMMUNITY - ABNORMAL IMMUNE-RESPONSES TO A BACTERIAL DNAJ ANTIGENIC DETERMINANT IN PATIENTS WITH EARLY RHEUMATOID-ARTHRITIS

A novel 'multistep molecular mimicry' mechanism for induction of rheum atoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously 'educated' by peptides derived from a class of human histo compatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli he at-shock protein dnaj. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from norma l subjects or controls with other autoimmune diseases do not. The acti vated T cells may cross-react with autologous dnaj heat-shock proteins that are expressed at synovial sites of inflammation. Our findings ma y have direct relevance to new strategies for the immune therapy of RA .