Biochemical Aspects of the Blood Group Rh (rhesus) Antigens

Despite their importance in clinical haematology, the details of the structures and possible functions of the proteins associated with Rh antigen expression have only recently begun to emerge. The antigens are carried by a multimeric complex between a M(r) 30,000 polypeptide which is not glycosylated (the Rh30 polypeptide), and a heavily glycosylated glycoprotein (the Rh50 glycoprotein). The N-terminal amino acid sequences of the two types of proteins were determined and used to isolated cDNA clones. The Rh30 and Rh50 proteins are both very hydrophobic membrane proteins, each containing up to 12 membrane spans. The two proteins are homologous in sequence and clearly belong to the same family. They are erythroid-specific and not related to any other known family of proteins. The Rh30 polypeptides are the genetic determinants of Rh blood group antigen activity. One polypeptide (Rh30A) is probably associated with CcEe antigen activity, while another (Rh30B) is responsible for the D antigen. The proteins have structures typical of transporters but their functions are still unclear. A number of other red cell membrane proteins (LW, CD47, glycophorin B and Fy) show alterations in red cells lacking Rh antigens (Rhnull). These proteins may have a role in the biosynthesis or function of the Rh30 and Rh50 proteins.