Allelic Sequence Variation in the HLA-DQ Region: Implications for Localization of Serological Specificities and for Susceptibility to Autoimmune Disease
The pattern of nucleotide sequence variation in the HLA-DQ genes has been analyzed with respect to the known serologically defined HLA types and to susceptibility to insulin-dependent diabetes (IDDM). Thus far, 8 allelic variants have been found for the DQα gene, and 12 alleles have been seen for DQβ. The DQw1 specificity correlates best with a related set of DQα variants, whereas the DQw2, DQw3, and DQ(blank) specificities correlate with alleles of DQβ. A pattern of amino acid substitutions at position 57 in the DQβ protein appears to reflect the degree of susceptibility to IDDM for the different HLA haplotypes. This portion of DQβ also shows significant homology with several human viruses, suggesting that it may be a preferred site for molecular mimicry.
KeywordsMolecular Mimicry Nonobese Diabetic Mouse Nucleotide Sequence Variation DQB2 Allele Haplotype Segment
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