HLA Class II DQ Epitopes.

Deng CT, Cai J, Tarsitani C, El-Awar N, Lachmann N, Ozawa M.

Clinical Transplants 2006, Chapter 9

Summary

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 no.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.