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Nat Immunol. 2001 Jun;2(6):501-7.

Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes.

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  • 1Laboratory of Molecular Medicine, The Department of Medicine, The Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA.

Erratum in

  • Nat Immunol 2001 Sep;2(9):889.

Abstract

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.

PMID:
11376336
[PubMed - indexed for MEDLINE]
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