Celiac disease (CD) is a chronic inflammatory disease of the small intestine that affects ∼1.5% of whites. A small number of gliadin and glutenin peptides derived from gluten elicit this inflammatory CD4+ T cell response. CD is predominantly limited to genetically predisposed individuals, namely those who express HLA-DQ2 (DQA1∗0501-DQB1∗0201) and/or HLA-DQ8 (DQA1∗0301-DQB1∗0302). A third haplotype associated with CD is found in patients who are HLA-DQ2+ and HLA-DQ8+. These individuals can produce the trans dimer, HLA-DQ8.5 (DQA1∗0501-DQB1∗0302), which is formed by the HLA-DQ2.5 α chain and the HLA-DQ8 β chain, and has a unique peptide-binding repertoire.