Susceptibility to murine and human insulin-dependent diabetes mellitus corr
elates strongly with major histocompatibility complex (MHC) class II I-A or
HLA-DQ alleles that lack an aspartic acid at position beta 57. I-A(g7) lac
ks this aspartate and is the only class II allele expressed by the nonobese
diabetic mouse. The crystal structure of I-A(g7) was determined at 2.6 ang
strom resolution as a complex with a high-affinity peptide from the autoant
igen glutamic acid decarboxylase (CAD) 65. I-A(g7) has a substantially wide
r peptide-binding groove around beta 57, which accounts for distinct peptid
e preferences compared with other MHC class II alleles. Loss of Asp(beta 57
) Leads to an oxyanion hole in I-A(g7) that can be filled by peptide carbox
yl residues or, perhaps, through interaction with the T cell receptor.