2NNA

Structure of the MHC class II molecule HLA-DQ8 bound with a deamidated gluten peptide

Summary for 2NNA

• Entry DOI: 10.2210/pdb2nna/pdb
• Descriptor: MHC class II antigen, gluten peptide, ... (4 entities in total)
• Functional Keywords: major histocompatibility complex hla-dq8, deamidated gluten peptide, post translational modification, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 46835.02

Authors

Henderson, K.N.,Tye-Din, J.A.,Rossjohn, J.,Anderson, R.P. (deposition date: 2006-10-24, release date: 2007-09-04, Last modification date: 2024-10-30)

Primary citation

Henderson, K.N.,Tye-Din, J.A.,Reid, H.H.,Chen, Z.,Borg, N.A.,Beissbarth, T.,Tatham, A.,Mannering, S.I.,Purcell, A.W.,Dudek, N.L.,van Heel, D.A.,McCluskey, J.,Rossjohn, J.,Anderson, R.P.
A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease
Immunity, 27:23-34, 2007

PubMed Abstract: The risk of celiac disease is strongly associated with human leukocyte antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the pathogenesis of HLA-DQ2-mediated celiac disease is established, the underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac pathology were indeed HLA DQ8 restricted and that multiple, mostly deamidated peptides derived from protease-sensitive sites of gliadin were recognized. This pattern of reactivity contrasted with the more absolute deamidation dependence and relative protease resistance of the dominant gliadin peptide in DQ2-mediated disease. We provided a structural basis for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The data established that the molecular mechanisms underlying HLA-DQ8-mediated celiac disease differed markedly from the HLA-DQ2-mediated form of the disease. Accordingly, nondietary therapeutic interventions in celiac disease might need to be tailored to the genotype of the individual.

PubMed: 17629515
DOI: 10.1016/j.immuni.2007.05.015

Experimental method

X-RAY DIFFRACTION (2.1 Å)