DQA1-ASTERISK-03 SUBTYPES HAVE DIFFERENT ASSOCIATIONS WITH DRB1 AND DQB1 ALLELES

Polymorphisms outside the hypervariable regions of HLA class II allele s that do not affect the peptide-binding site are probably not under s elective pressure and could therefore be useful as markers of the evol utionary pathways of the HLA class II haplotypes. We have analyzed suc h a polymorphism in the variants of DQA103, which differ at residue 1 60 encoded in exon 3. Our study included homozygous BCLs of the 10th I HWS and samples of a multiracial panel of 723 unrelated subjects which were also typed for allelic variations in exon 2 by hybridization wit h SSOP. BCLs having DQA103 and 131 selected DQA1*03-positive samples were typed for the dimorphism in exon 3 that distinguishes DQA10301 a nd DQA10302. DQA1*0301 was found to be exclusively associated with DQ B10302, while samples carrying DQB1*0201, 0301, 0303, and 0401 always had DQA10302. A few haplotypes carrying DQB1*0302 had DQA1*0302. The fact that DQA10301 is completely included in DQB1*0302, and not vice versa, suggests that DQA10301 may have arisen from a mutation in a h aplotype containing DQA10302-DQB1*0302. DQB1*0302 was found to be ass ociated with all DR4 subtypes, suggesting possibly that the current va riants of DRB1-DR4 may be of more recent origin. DRB10405 was the onl y subtype of DR4 which was not associated with DQA10301 and had multi ple associations with the DQB1 alleles, therefore, perhaps representin g the oldest allele of this group.