HLA class II DQ epitopes.

1. DQ epitopes were defined by studying the distinct reaction profiles of 17 allosera and 35 DQ-specific mouse monoclonal antibodies to HLA class II single antigen beads coated with purified recombinant DQ molecules. 2. DQ molecules are heterodimers with a polymorphic alpha chain and beta chain. Sixteen of the defined epitopes correlated to various DQB specificities and one defined epitope correlated to DQA1*0201. 3. Among the 16 DQB epitopes, 7 sites were recognized by both alloantibodies and DQ monoclonal antibodies, 5 sites were identified by DQ monoclonal antibodies and 4 sites by alloantibodies. The only unequivocal DQA1*0201 epitope found was identified by an alloantibody from a patient with a failed kidney graft. 4. Of the 17 DQ epitopes, 10 sites have a very restricted possible choice involving one to three amino acid(s) to form the unique sites; while the other 7 sites (6 DQB sites and 1 DQA site) have multiple potential sites. 5. The amino acid residues for all of 16 DQB epitope sites are unique and not shared with DQA, DR or DP antigens; while the DQA1*0201 epitope site is not shared with DQB, DR or DP antigens. 6. Except epitope #2008, all the other 16 epitopes consist of unique amino acids that appear to be exposed on the surface of DQ molecules as viewed from the 3-D model. 7. The existence of antibodies to multiple epitopes on the same HLA molecule invites molecular epitope analysis of serum reaction profiles. A single antigen cannot be considered to be a single epitope.