The invention provides anti-HLA-DQ2.5/8 antibodies and methods of using the same. The antibodies of the present invention have binding activity to human HLA-DQ2.5/8 and monkey MHC-DQ, but substantially no binding activity to HLA-DR, HLA-DP, or a complex of the invariant chain (CD74) and HLA-DQ2.5/8. The antibodies bind to HLA-DQ2.5/8 in the presence of a gluten peptide such as gliadin, i.e., bind to HLA-DQ2.5/8 forming a complex with the gluten peptide. The antibodies have neutralizing activity against the binding between HLA-DQ2.5/8 and TCR, and thus block the interaction between HLA-DQ2.5/8 and an HLA-DQ2.5/8-restricted CD4+ T cell. The antibodies do not undergo rapid internalization mediated by the invariant chain. These characteristics are particularly useful for treating celiac disease. Thus, the present invention also provides a method of treating celiac disease using the antibodies of the present invention.
