Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes.
The class II major histocompatibility complex (MHC) glycoproteins HLA-DQ8 and HLA-DQ2 in humans and I-A(g7) in nonobese diabetic (NOD) mice are the major risk factors for increased susceptibility to type 1 diabetes. Using X-ray crystallography, we have determined the three-dimensional structure of DQ8 complexed with an immunodominant peptide from insulin. The similarity of the DQ8, DQ2 and I-A(g7) peptide-binding pockets suggests that diabetes is caused by the same antigen-presentation event(s) in humans and NOD mice. Correlating type 1 diabetes epidemiology and MHC sequences with the DQ8 structure suggests that other structural features of the P9 pocket in addition to position 57 contribute to susceptibility to type 1 diabetes.[1]References
- Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes. Lee, K.H., Wucherpfennig, K.W., Wiley, D.C. Nat. Immunol. (2001) [Pubmed]
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