Histocompatibility leukocyte antigen DQ molecules exhibit polymorphism of both DQ alpha- and beta-chains. Histocompatibility leukocyte antigen-DQw3 is associated with both DR4 and DR5 and can be further subdivided by reactivity with the monoclonal antibody TA10. To determine the molecular nature of the DQ polymorphic alleles associated with the DR4 haplotype, we have sequenced and analyzed DQ alpha and beta cDNA clones obtained from a DR4, Dw4, DQw3 cell line which is TA10-positive. The DQ alpha-chain sequence was identical to previously published sequences from the DR4 haplotype, but the DQ beta sequence differed from published DR4-DQ beta sequences obtained from DQw3-positive TA10-negative cell lines by eight amino acids, six of which were located in the beta 1 domain. Thus, the TA10 serologic determinants reside on the DQ beta-chain. A TA10-specific oligonucleotide probe was constructed based on the DQ beta sequence, and its specificity was confirmed in a panel of TA10-positive and TA10-negative cell lines. An additional band was observed in Southern blotting experiments which may indicate a donor sequence for gene conversion.