Development of nondonor-specific HLA-DR antibodies in allograft recipients is associated with shared epitopes with mismatched donor DR antigens.

Our previous studies showed that not only donor-specific antibodies (DSA) but also nondonor-specific antibodies (NDSA) were detected in the peripheral blood of allograft recipients. The molecular mechanism involved in the development of NDSA is examined here. HLA class II single antigen (SA) beads were used to determine the presence of HLA DR-specific antibodies in renal transplant recipients with failed allografts. Sequence-based antibody-epitope mapping was determined by the comparison of the reaction profiles of different SA recombinant cell lines containing unique epitope pattern. We found that 22 out of 65 recipients with failed grafts developed antibodies against donor HLA DR that is a mismatch with the recipient. Three of them had only DSA while 19 patients had not only DSA but also NDSA. An average of 77.3% of NDSA reacted with targets that share amino acid sequence with mismatched donor DR antigens. Either surface or nonsurface amino acid residues may constitute an antibody epitope. In conclusion, development of NDSA in allograft recipients may be associated with shared amino acids with mismatched donor antigens. SA beads technique not only helps to determine antibody specificities but also provides an ideal approach for the identification of potential HLA antibody epitopes.