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- Title
Structure of a human insulin peptide?HLA-DQ8 complex and susceptibility to type 1 diabetes.
- Authors
Lee, Kon Ho; Wucherpfennig, Kai W.; Wiley, Don C.
- Abstract
The class II major histocompatibility complex (MHC) glycoproteins HLA-DQ8 and HLA-DQ2 in humans and I-Ag7 in nonobese diabetic (NOD) mice are the major risk factors for increased suscepti-bility to type 1 diabetes. Using X-ray crystallography, we have determined the three-dimen-sional structure of DQ8 complexed with an immunodominant peptide from insulin. The similarity of the DQ8, DQ2 and I-Ag7 peptide-binding pockets suggests that diabetes is caused by the same antigen-presentation event(s) in humans and NOD mice. Correlating type 1 diabetes epidemio-logy and MHC sequences with the DQ8 structure suggests that other structural features of the P9 pocket in addi-tion to position 57 contribute to susceptibility to type 1 diabetes.
- Subjects
MAJOR histocompatibility complex; GLYCOPROTEINS; DIABETES
- Publication
Nature Immunology, 2001, Vol 2, Issue 6, p501
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/88694