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ß Protein Dimer, the Class II MHC Allele Associated with Protection from Insulin-Dependent Diabetes Mellitus1
*
Virginia Mason Research Center and
Department of Immunology, University of Washington School of Medicine, Seattle, WA 98101
Studies of the stability of HLA-DQ have revealed a correlation
between SDS stability of MHC class II 
ß dimers and
insulin-dependent diabetes mellitus (IDDM) susceptibility. The MHC
class II ß dimer encoded by HLA-DQA1*0102/DQB1*0602 (DQ0602),
which is a dominant protective allele in IDDM, exhibits the greatest
SDS stability among HLA-DQ molecules in EBV-transformed
B-lymphoblastoid cells and PBLs. DQ0602 is also uniquely SDS stable in
the HLA-DM-deficient cell line, BLS-1. We addressed the molecular
mechanism of the stability of DQ0602 in BLS-1. A panel of mutants based
on the polymorphic differences between HLA-DQA1*0102/DQB1*0602 and
HLA-DQA1*0102/DQB1*0604 were generated and expressed in BLS-1. An Asp
at ß57 was found to be critical for SDS stability, whereas Tyr at
ß30, Gly at ß70, and Ala at ß86 played secondary roles.
Furthermore, the level of class II-associated invariant chain peptide
bound to HLA-DQ did not correlate with SDS stability, suggesting that
class II-associated invariant chain peptide does not play a direct role
in the unique SDS stability of DQ0602. These results support a role for
DQB1 codon 57 in HLA-DQ ß dimer stability and IDDM
susceptibility.
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