New insight into the Rh system: structure and function

Since the inception of the molecular era of Rh biology in the early 1990s with the cloning of Rh CcEe [1,2], D [3,4] and RhAG [5] cDNAs, there has been a large degree of speculation concerning the function and molecular assembly of the Rh protein complex. This is for two important reasons: the Rh antigens are of considerable importance in transfusion medicine and are of functional and structural significance to the red cell membrane, as Rh-null erythrocytes that lack all proteins of the Rh complex have key structural and biochemical anomalies. In this review I will consider recent advances in our understanding of Rh structure, and indicate how this relates to function. As has been historical since the discovery of the Rh system in 1939, there is some controversy surrounding current ideas of both structure and function(s) and I will attempt to provide a balanced viewpoint on this debate. The reader is referred to several comprehensive reviews on the molecular biology and genetics of the Rh blood group system which deal in much greater depth with the clinical significance and molecular basis of Rh alleles [6-9].