Molecular Mimicry and T Cell–mediated Autoimmune Disease

Both T cell tolerance and productive T cell responses require the interaction of the TCR with specific MHC–peptide ligands, triggering a cascade of signals that ultimately can lead to either proliferation or cell death (1– 3). These two opposing processes, which can occur during both peripheral T cell activation and/or positive/negative selection of T cells in the thymus, seem to be tuned by two different mechanisms: either by the strength of avidity/affinity of the TCR for their ligands, or by the differential changes in the conformation or orientation of the TCR after its ligation on the MHC–peptide complexes (4, 5). Recently, the outcomes of T cell activation in periphery or of thymic selection have been related to the agonist or antagonist activity of MHC peptide ligands for the TCR; the agonist ligands, having high affinity for the TCR (slow dissociation), would promote deletion in the thymus...