The primary structure of a variant HLA-B8 antigen has been determined by cDNA cloning and sequencing. The variant, B*0802 differs, from the common B*0801 subtype at positions 77-83 of the alpha 1 helix that determine the Bw4 and Bw6 public epitopes. Whereas B*0801 has the common Bw6 motif, B*0802 has the Bw4 motif found in B*13 and B*44 allotypes. Serological analysis of B cell lines expressing B*0802 and of a B*0802 transfectant made with the HLA-A,B negative cell line 721.221 shows that B*0802 reacts with Bw4-specific antibodies, but at a level much lower than expected for Bw4 positive HLA-B allotypes.