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In 1939 Levene and Stetson reported a maternal antibody directed against paternally derived fetal antigens. The following year Landsteiner and Weiner immunised rabbits with Rhesus macaque monkey sera, the resultant antisera seemed to share specificity with that of the antibodies found by Levene and Stetson and was found to bind a previously unidentified human blood group antigen which was thus named the Rh (Rhesus) antigen. The anti-Rh antibodies also seemingly shared specificity with those of patients suffering transfusion reactions (Weiner and Peters, 1940) and so it was assumed that the human homologue of the rhesus maqaque antigen had a significant bearing on the safety of blood transfusions. It was subsequently found that a separate protein bore the antigen identified by Levene-Stetson and Weiner-Peters (i.e. that of the fetal and transfusion complications) in human subjects but was strongly associated with another human protein that defined the Rhesus monkey antigen homologue identified by Landsteiner and Weiner. By this point the medical significance (in terms of transfusion medicine) had entrenched the terminology - the term 'Rh' was inseparable with the former antigen - and so the nomenclature, although misleading, remained and the Rhesus monkey antigen homologue was dubbed the LW (Landsteiner and Weiner) antigen.

The Rh blood group system is one of the most polymorphic and immunogenic systems known at this time in humans. It is controlled by two genes, that encode two distinct Rh proteins. One protein carries the C/c and E/e antigens, and is therefore called the Rh CE or Rh ce (or Rh Ce or Rh cE) protein. The other carries the Rh D antigen, and is called Rh D protein. A fourth Rh antigen, Rh G, is located partly on the Rh CE and partly on the Rh D protein.

The genes encoding these two proteins have been cloned, end the molecular basis of the immunogenicity is being studied extensively world wide.

Rh D is a protein that sits in the plasma membrane of red blood cells. It crosses the membrane 12 times, creating 6 extracellular loops, and 5 intra cellular loops. Both the carboxy- and the amino-tail of the protein stick out into the interior of the cell.

The presence or absence of the Rh D protein from red blood cells determines if one is typed Rh+ (protein is present) or Rh- (protein is absent).

The Rh D blood group system is the second most immunogenic system known at this time. Only the ABO system has greater clinical importance.

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