To determine whether a correlation exists between the genomic HLA class II DP DNA polymorphism and cell surface expression and to detect the DP epitopes responsible for alloreactivity, anti-DP T-cell clones were generated against new PLT blank RFLP DPa and DPb-defined specificities. The clones were tested on the 10th IHWS B-LCLs and on local panel cells. Oligotyping of the tested cells made it possible to (a) correlate the DPa specificity with the DPB1*0402 specificity and (b) split DPb into DPB1*1001 and DPB1*1401. By comparing DNA sequences of the second exon to panel reactivity, the epitopes responsible for DPB1*1001 and 1401 were defined and attributed to beta-chain residues contributing to peptide selection inside the HLA groove. However, DNA sequences could not explain anti-DPa allospecificity, indicating that another structure not yet definable may be involved.