Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility totype I diabetes

Citation
Kh. Lee et al., Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility totype I diabetes, NAT IMMUNOL, 2(6), 2001, pp. 501-507
Citations number
74
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
NATURE IMMUNOLOGY
ISSN journal
1529-2908 → ACNP
Volume
2
Issue
6
Year of publication
2001
Pages
501 - 507
Database
ISI
SICI code
1529-2908(200106)2:6<501:SOAHIP>2.0.ZU;2-6
Abstract
The class II major histocompatibility complex (MHC) glycoproteins HLA-DQ8 a nd HLA-DQ2 in humans and I-A(g7) in nonobese diabetic (NOD) mice are the ma jor risk factors for increased susceptibility to type I diabetes. using X-r ay crystallography, we have determined the three-dimen-sional structure of DQ8 complexed with an immunodominant peptide from insulin. The similarity o f the DQ8, DQ2 and I-A(g7) peptide-binding pockets suggests that diabetes i s caused by the same antigen-presentation event(s) in humans and NOD mice. Correlating type I diabetes epidemiology and MHC sequences with the DQ8 str ucture suggests that other structural features of the P9 pocket in addition to position 57 contribute to susceptibility to type I diabetes.