The initiation and early development of autoimmune diseases

Our understanding of autoimmunity has changed considerably over the past years as a consequence of the demonstration that self-reactive B cells and T cells are not necessarily deleted from the immunological vocabulary. The critical event in initiating (or avoiding) autoimmune responses is presentation to T cells of the self-peptide-MHC antigen complex. Based on the premise that quantitative aspects are of paramount importance, we suggest that T-cell activity, MHC expression, and self-peptide binding determine the initiation of autoimmune responses.