A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes.
Science
; 288(5465): 505-11, 2000 Apr 21.
Article
em En
| MEDLINE
| ID: mdl-10775108
ABSTRACT
Susceptibility to murine and human insulin-dependent diabetes mellitus correlates strongly with major histocompatibility complex (MHC) class II I-A or HLA-DQ alleles that lack an aspartic acid at position beta57. I-Ag7 lacks this aspartate and is the only class II allele expressed by the nonobese diabetic mouse. The crystal structure of I-Ag7 was determined at 2.6 angstrom resolution as a complex with a high-affinity peptide from the autoantigen glutamic acid decarboxylase (GAD) 65. I-Ag7 has a substantially wider peptide-binding groove around beta57, which accounts for distinct peptide preferences compared with other MHC class II alleles. Loss of Asp(beta57) leads to an oxyanion hole in I-Ag7 that can be filled by peptide carboxyl residues or, perhaps, through interaction with the T cell receptor.
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Base de dados:
MEDLINE
Assunto principal:
Antígenos de Histocompatibilidade Classe II
/
Genes MHC da Classe II
/
Diabetes Mellitus Tipo 1
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article