HLA-DQw3-related determinants: analysis of subunit and spatial relationships

More polymorphism exists among DQ region gene products than is suggested by present serologic definitions of these class II molecules. DQ beta polymorphism among haplotypes carrying the DQw3 specificity is considerable. The TA10 specificity is present on one allele of at least three different DQ beta alleles that carry the DQw3 specificity. We have examined a series of monoclonal antibodies directed against different DQ beta alleles carrying the DQw3 specificity to determine subunit and spatial relationship among the epitopes detected by these antibodies. The antibodies were examined by Western blotting and for their ability to inhibit the binding of fluoresceinated antibodies on either TA10+ or TA10- DQw3 haplotypes. Our results reveal that (1) multiple DQw3-related epitopes exist; (2) several anti-DQw3-related antibodies generated against TA10- DQw3 molecules are unable to inhibit the binding of a TA10-specific antibody on a TA10+ haplotype while strongly inhibiting binding of an antibody detecting the reciprocal DQ beta polymorphism on a TA10- DQw3 haplotype; and (3) there is a strong requirement for three-dimensional conformation in the formation of the majority of the epitopes examined here. Analysis of previously published amino acid sequences for the haplotypes investigated here suggest that charge changes at amino acids 45, and 57, respectively, may have a significant effect in changing the spatial relationship between the DQw3-related epitope(s) and other polymorphic determinants on DQ beta chains.