It has long been known that relative immunogenicity is a characteristic of protein red blood cell (RBC) antigens, but the mechanisms remain unclear. The aim of this work was to elucidate the mechanisms underlying this relative immunogenicity.STUDY DESIGN AND METHODS
Two RBC antigens were used as a model—the highly immunogenic K antigen (KEL1) and the less immunogenic Fya antigen (FY1)—and analyzed the distribution of DRB1* molecules in two groups of Caucasian individuals producing anti-Fya (n = 29) or anti-K (n = 30) alloantibodies. These experimental results were compared to the results generated by TEPITOPE, a DRB1* peptide–binding motif prediction algorithm.RESULTS
It was found that within the anti-Fya group, the DRB1*04 phenotypic frequency was 100 percent, indicating that the DRB1*04 molecule is the restriction molecule. In the anti-K group, numerous DRB1* molecules were identified, demonstrating a high degree of histocompatibility promiscuity, corresponding to the predominant molecules in the Caucasian population. These findings were confirmed by TEPITOPE.CONCLUSION
These results strongly suggest that protein RBC intrinsic immunogenicity depends on the distribution of DRB1* restriction molecules.