Involvement of Ser103 of the Rh polypeptides in G epitope formation

Background: Almost all red cells that carry D and/or C antigens also express the G antigen (Rh12). A study was conducted on the molecular background of the G epitope. Study Design and Methods: Two unrelated donors with the rare ccDEe, G- phenotype and one donor with the ccEe, G+ phenotype were studied. Genomic DNA and cDNA of these donors were studied with polymerase chain reaction, Southern blot, and sequence analysis, with special focus on exon 2, because it is only in this exon that there are supposed to be similarities between RHD and the RHC allele, but not between RHD and the RHc allele. Results: In both ccDEe, G- donors, a nucleotide substitution was found in exon 2 of RHD; T307 was replaced by C307, which predicted a Ser-->Pro substitution at amino acid position 103 of the D polypeptide. The ccEe, G+ donor carried the complete exon 2 of RHD. Moreover, despite the absence of all known D epitopes, this donor also carried RHD characteristics in exons 1 to 3 and exon 9 and further downstream. Conclusion: Ser103, encoded by exon 2 of the RH genes, is involved in G epitope formation.