The major histocompatibility complex (MHC) on human chromosome 6 represents the most important genetic locus for a number of common human autoimmune diseases. Specific alleles that differ from closely related alleles by only one or a few amino acids in the peptide binding groove are frequently strongly associated with disease susceptibility, raising the important question of which peptide presentation events are critical in disease initiation and progression. This review will cover a number of topics pertinent to this fundamental question, including MHC linked disease susceptibility to autoimmune diseases, molecular mechanisms for the role of MHC molecules in autoimmune diseases as well as the recognition of self and microbial peptides by self-reactive T cell receptors (TCRs).
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