Characterization of Seven Low Incidence Blood Group Antigens Carried by Erythrocyte Band 3 Protein

Abstract

Recent studies have demonstrated that band 3 carries antigens of the Diego blood group system and have elucidated the molecular basis of several previously unassigned low incidence and high incidence antigens. Because the available serological data suggested that band 3 may carry additional low incidence blood group antigens, we screened band 3 genomic DNA encoding the membrane domain of band 3 for single-strand conformational polymorphisms. We found that the putative first ectoplasmic loop of band 3 carries blood group antigen ELO, 432 Arg→Trp; the third putative loop harbors antigens Vga (Van Vugt), 555 Tyr→His, BOW 561 Pro→Ser, Wu (Wulfsberg), 565 Gly→Ala, and Bpa (Bishop), 569 Asn→Lys; and the putative fourth ectoplasmic loop carries antigens Hga (Hughes), 656 Arg→Cys, and Moa (Moen), 656 Arg→His. We studied erythrocytes from carriers of five of these blood group antigens. We found similar levels of reticulocyte mRNA corresponding to the two band 3 gene alleles, normal content and glycosylation of band 3 in the red blood cell membrane, and normal band 3-mediated sulfate influx into red blood cells, suggesting that the mutations do not have major effect on band 3 structure and function. In addition to elucidating the molecular basis of seven low incidence blood group antigens, these results help to create a more accurate structural model of band 3.

Membrane-anchored carbonic anhydrase IV interacts with monocarboxylate transporters via their chaperones CD147 and GP70

“…However, if we assume that binding between AE1 and CAIV follows the same principle as binding between CD147/GP70 and CAIV, CAIV-His-88 might either bind to Arg-656 or Glu-658 in AE1. Interestingly, both Arg-656 and Glu-658 are subject to point mutations that induce blood group antigens (Mo a (R656H), Hg a (R656C), and Wr a (E658K) (68,69)). Corresponding to the findings in this study, mutation of AE1-Arg-656 to either cysteine or histidine could be predicted to lead to a loss of binding between AE1 and CAIV, which would result in functional impairment of AE1 transport activity, whereas mutation of AE1-Glu-658 to lysine should still allow binding between transporter and enzyme, without affecting AE1 transport function.…”

Red cell antibody screening in South India: lessons learnt

“…The relative frequency of missing clinically significant antibodies was found to be very small ranging from 1/1744 to 1/11 595 [9,10]. These did not pose any problem in routine transfusions, as most donors possibly lacked the corresponding rare antigens [11].…”

Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

“…However, RBC alloantigenicity depends primarily on residues/modifications exposed to the extracellular milieu, regardless of their role in expression, localization, or function. Many blood group antigenic sites will not be subject to strong evolutionary pressure, as described previously for Diego 62 and Kell. 63 Biochemical differences in amino acid substitutions may also not be as critical for immunohematology, since several proven antigenic variations (Wu/DISK, KEL:-22, KUCI-, Co(b+), etc) result from amino acid substitutions that are considered "conservative."…”