Autoantigen processing and the mechanisms of tolerance to self.

Large foreign protein antigens are processed in antigen presenting cells before they can be recognized by T lymphocytes. The processing involves the ingestion of the antigen, a controlled proteolytic fragmentation, and the association of immunogenic fragments with MHC class II molecules. The processing provides for exposure to the T lymphocytes of the immune system of epitopes which are buried in the interior of globular protein. Here we argue that autologous molecules (i.e., autoantigens) are also processed and that this applies to intracellular molecules as well as to plasma membrane proteins and tissues and serum proteins. The implication is that autoimmune T lymphocytes recognize fragments of self molecules in the context of MHC molecules and that autotolerance is toward these same epitopes.