BriefDefinitive Report HLA-DQ POLYMORPHISM ASSOCIATED WITH RESISTANCE TO TYPE I DIABETES DETECTED WITH MONOCLONAL ANTIBODIES, ISOELECTRIC POINT DIFFERENCES, AND RESTRICTION FRAGMENT LENGTH POLYMORPHISM

Recently (1), we described a new genetic system that is HLA-DQ-related . Two alleles, 2B3 and TA10, can be recognized serologically . The 2133 specificity detected with the 11133 mAb was previously described (2) as a DQwl-related specificity . The TA 10 specificity is DQw3-related and was first. described by Maeda (3) with the TA 10 mAb. TA10 can also be detected with alloantisera (4) . Recently, an absolute correlation of the TA10 specificity with a RFLP using a DQ(O probe has been described (5). The 2133 and TA 10 determinants are in linkage disequilibrium with HLA-DR specificities . Both specificities are positively associated with DR4 but never occur together on the same haplotype (1) . DR3+, DQw2' haplotypes carry neither 2133 nor TA 10 . We wanted to know the molecular localization of these epitopes . Bontrop et al . (6) saw a polymorphism similar to 2133/TA10 in a study where DQ molecules isolated from DR4 homozygous typing cells (HTC) focused in different positions . Furthermore, Tilanus et al . (7) studied RFLP obtained after digestion with various restriction enzymes and hybridization with a DQO probe. Within a group of DR4 HTCs, specific fragments were observed, the presence of which closely associated with both the 2133/TA10 polymorphism as well as the IEF experiments. The pertinent data showing the nearly perfect correlation between the mAbs, IEF, and RFLP will be summarized in this paper. The 2B3/TA10 polymorphism is apparently independent from HLA-D, at least in DR4 haplotypes (6, 7) . Furthermore, it is genetically determined and linked to HLA, as shown by family segregation studies (1) . The segregation of specific DNA fragments with 2133 and TA10 was also shown in a family where the mother was DR3 homozygous, negative for 2133 and TA10, and lacked the specific DNA fragments in RFLP (7). The father was DR4 homozygous and positive for both