The D antigen comprises a mosaic of many epitopes. Most D-positive individuals have normal D antigens with all epitopes present, but there are some persons with rare D-positive red cells in which some D epitopes are missing. If immunized with normal D-positive red cells, individuals with partial D can make antibody to those D epitopes which they lack. This antibody will not react with their own cells, or with partial D red cells of the same type, but will behave as anti-D when tested with red cells of common Rh phenotypes. In some cases, the D epitopes of a partial D antigen will be expressed weakly, and the term partial weak D applies. Over 20 different types of partial D have been
D-negative represents the absence of the whole RhD protein from the membrane and anti-D can detect epitopes on any of the external loops of the RhD protein. D-positive people may be homozygous or hemizygous for the presence of RHD. Most D-negative black Africans, however, have an inactive RHD, called the RHD-pseudogene (RHDyf), that contains a 37-basepair duplication in exon 4 and a translation stop codon in exon 6.
The Cc polymorphism is associated with three or four amino acid substitutions encoded by exons 1 and 2 of RHCE, although the definitive change is Ser103 for C and Pro103 for c in the second extracellular loop of the RhCcEe protein. E and e are associated with Pro226 and Ala226, respectively, in the fourth extracellular loop.
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