Relative immunogenicity of Fya and K antigens in a Caucasian population, based on HLA class II restriction analysis

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.

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.

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.

These results strongly suggest that protein RBC intrinsic immunogenicity depends on the distribution of DRB1* restriction molecules.