Genetic polymorphisms of the HLA-DPB1 gene in Japanese and Caucasian panel cells defined by PLT were analyzed by the PCR-based genotyping technique PCR-RFLP, and suballeles of DPw3 (DPB1*03) and DP"Cp63" (DPB1*09) could be detected. PLT-defined DPw3 cells were typed by PCR-RFLP as either DPB1*0301 or DPB1*1401. On the other hand, PLT-defined DPCp63-typed cells were typed as DPB1*0901 or DPB1*1001. These results indicate that both DPw3 and DPCp63 are split into two subantigens. DPw2 and DPw4 are DPB1*0201 and 0202 and DPB1*0401 and 0402, respectively. Comparative analysis of the amino acid sequences of the DPw2-, DPw4-, DPw3-, and DPCp63-associated alleles revealed that the fourth (C), fifth (D), and sixth (E) hypervariable regions at amino acid positions 65-87 were shared within the same PLT-defined DP antigen groups, suggesting that these three hypervariable regions are recognized by cloned T cells in PLT, thus determining DP antigen specificity. On the basis of this model, 44 DPB1 alleles can be classified into 18 antigen groups, each of which may possibly represent a PLT-defined single DP specificity.