Abstract
Many autoimmune diseases are associated with specific alleles of the major histocompatibility complex (MHC), but how a particular MHC allele contributes to a particular disease is often not known. The MHC class II allele HLA-DQ8 has been linked to celiac disease, an autoimmune disease driven by T cell responses against dietary gluten, as occurs in wheat, for example. In contrast to other MHC alleles, HLA-DQ8 lacks an aspartic acid residue in its peptide-binding pocket and thus preferentially binds to peptides and T cell receptors (TCRs) that carry a negative charge. In celiac disease, negatively charged gluten-derived peptides are generated by tissue transglutaminase (which converts glutamine to glutamic acid); however, how HLA-DQ8 contributes to disease is not clear because transglutaminase requires inflammation for its activation.
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