CHANGES IN THE BLOOD-GROUP WRIGHT ANTIGENS ARE ASSOCIATED WITH A MUTATION AT AMINO-ACID-658 IN HUMAN ERYTHROCYTE BAND-3 - A SITE OF INTERACTION BETWEEN BAND-3 AND GLYCOPHORIN-A UNDER CERTAIN CONDITIONS

The Wright (Wr) blood group antigens, Wr(a) and Wr(b), have been sugge sted to be determined by alleles of the same gene. The Wr(b) antigen a ppears to involve both red blood cell (RBC) band 3 and glycophorin A ( GPA). We have examined the cDNA sequences of the band 3 and GPA of one of the two known Wr(a+b-) individuals. We show that this individual i s homozygous for the mutation Glu(658) --> Lys in band 3, but has norm al GPA. Putative heterozygotes with Wr(a+b+) RBCs have both Glu and Ly s at residue 658 of band 3, whereas the common Wr(a-b+) RBC phenotype only have band 3 with Glu(658). The Wr(a) and Wr(b) antigens are deter mined by the amino acid at residue 658 of band 3 and are antithetical. Examination of the amino acid sequence and Wr(b) antigen expression o f GPA-related hybrid glycophorins suggests that Arg(61) of GPA interac ts with Glu(658) of band 3 to form the Wr(b) antigen. We suggest that the interaction is stabilized by the presence of anti-Wr(b) antibodies and that this site of association between GPA and band 3 may be respo nsible for the previously reported ability of anti-GPA antibodies to d ecrease the deformability of RBCs. (C) 1995 by The American Society of Hematology.