The HLA-DP alpha chain-specific monoclonal antibody DP11.1 binds only to the surfaces of cells types as DPw2 or DPw4 by primed lymphocyte typing. To investigate the molecular basis for this antibody binding specificity, we isolated a DPw3 alpha chain cDNA clone and compared its sequence to those of other published DP alpha chain alleles. Interestingly, the extracellular region of the DPw3 alpha chain was identical to the analogous regions of DPw2 and DPw4 alpha chains. Immunoblotting analysis confirmed that the DP11.1 epitope is conserved on denatured DP alpha chains associated with cells typed as DPw2, DPw3, and DPw4. Therefore the binding of antibody DP11.1 to its alpha chain epitope is influenced by the associations between the DP alpha chain and its polymorphic DP beta chain partner.