Structure of a human insulin peptide–HLA-DQ8 complex and susceptibility to type 1 diabetes
- 1 June 2001
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 2 (6) , 501-507
- https://doi.org/10.1038/88694
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.Keywords
This publication has 68 references indexed in Scilit:
- Mutations Changing the Kinetics of Class II MHC Peptide ExchangeImmunity, 2001
- A disease-associated cellular immune response in type 1 diabetics to an immunodominant epitope of insulinJournal of Clinical Investigation, 2001
- Structural basis for the binding of an immunodominant peptide from myelin basic protein in different registers by two HLA-DR2 proteinsJournal of Molecular Biology, 2000
- Dual Overlapping Peptides Recognized by Insulin Peptide B:9–23 T Cell Receptor AV13S3 T Cell Clones of the NOD MouseJournal of Autoimmunity, 2000
- HLA class II immunogenetics of IDDM in Yemenite JewsHuman Immunology, 1998
- HLA Class II region nucleotide sequences, 1995Tissue Antigens, 1995
- The distribution of DR4 haplotypes in sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 lociHuman Immunology, 1995
- Epitope specificity, cytokine production profile and diabetogenic activity of insulin‐specific T cell clones isolated from NOD miceEuropean Journal of Immunology, 1995
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994
- Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1Nature, 1993