Insights into autoimmunity gained from structural analysis of MHC-peptide complexes

The structural and functional properties of HLA-DQ and -DR molecules that c onfer susceptibility to several common autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis, have been defined. T he relevant polymorphisms directly affect interaction with peptides, which provides strong support for the hypothesis that these diseases are peptide- antigen driven. Several studies indicate that structural modifications of p eptides can affect MHC class II binding and/or TCR recognition and should b e considered in the analysis of T cell responses in autoimmune diseases.