One striking aspect of many autoimmune diseases is their association with particular HLA class II alleles. A high frequency of certain major histocompatibility class II alleles has been found in both T cell-mediated and autoantibody-mediated autoimmune diseases. In certain autoimmune diseases, such as rheumatoid arthritis, there is association with two or more MHC class II alleles. Examination of the amino acid sequences of autoimmune disease-associated class II molecules has revealed that they share or are identical in those polymorphic residues which govern the binding of immunogenic peptides'. Thus it seems reasonable to postulate that the underlying basis for disease association is the preferential binding of autoantigenic peptides by the disease-associated class II allele and their presentation to autoreactive T cells.