A new human Duffy blood group specificity defined by a murine monoclonal antibody. Immunogenetics and association with susceptibility to Plasmodium vivax.

Abstract

The Duffy blood group system of human erythrocytes comprises a membrane glycoprotein recently characterized by immunoprecipitation techniques (1). It is a polymorphic system that includes determinants for five alloantigens, two of which are Mendelian alleles (Fya and Fyb) (2, 3). A null genotype, designated Fy(a b-) (4), lacks the expression of both Fya and Fy b, and is inherited as a third allele of the series . Homozygous Fy(a-b-) red cells, however, also lack expression of the Fy3 (5) antigen, which is present on all other Duffy types. Fy4 (6) occurs on almost all samples of Fy(a b-), but the expression is weak on some . In addition Fy4 is occasionally found on red cells of Fy(a +b'), so that its exact Duffy status is not in perfect agreement with the absence of both Fya and Fy b (7). Fy5 (8) resembles Fy3 but is also absent from Rh-null red cells regardless of their other Duffy types.These five specificities are inherited en bloc but they differ in their susceptibility to proteolytic enzyme treatment; the high frequency antigens Fy3, Fy4, and Fy5 being resistant to the effects of chymotrypsin, ficin, and papain, while Fya and Fy b are completely destroyed by these enzymes (7). Duffy maps to chromosome 1 (9) (i.e., is syntenic to Rh), which may be related to the peculiar absence of Fy5 on Rh-null cells.Interest in the Duffy system has been considerable since the demonstration by Miller et al . (10) We have prepared a murine monoclonal antibody, anti-Fy6, that reacts with all human red cells except for those of the Fy(ab-) phenotype. The specificity defined by anti-Fy6 differs significantly from others previously identified in the Duffy system . In this report we show that Fy6 is not only characteristic of Duffy, but is related to the penetration of red cells by P. vivax merozoites. 776J. Exp. MED.

Hemopoietic Cell Expression of the Chemokine Decoy Receptor D6 Is Dynamic and Regulated by GATA1

“…Thus, our observations may suggest some variability in the epitopes revealed by D6 on LECs and leukocytes reflecting previous precedents within the chemokine receptor field which indicate that different cell staining results for a single receptor can be obtained using different clones of mAbs (46). Similar differential Ab specificities have also been demonstrated for another atypical chemokine receptor, DARC, which has a number of antigenic epitopes detected by a range of different Abs in alternative cellular contexts (47)(48)(49).…”

A Receptor for the Malarial Parasite Plasmodium vivax : the Erythrocyte Chemokine Receptor

“…Second, both proteins aggregate to a high molecular weight complex in SDS-polyacrylamide gels when boiled in SDS-2-mercaptoethanol (11,12). Third, the number of chemokine receptor binding sites detected by radiolabeled IL-8 binding is about the same as the number of Duffy blood group antigens detected by antibody (5,000 to 10,000 per cell) (1,2,13). Fourth, both proteins are resistant to degradation by treatment of intact erythrocytes with trypsin; both are degraded by treatment of erythrocytes with chymotrypsin (1,11).…”

“…A monoclonal antibody to the Duffy blood group antigen, anti-Fy6 (13), which inhibits the binding of the P. knowlesi ligand (14), was tested for its ability to inhibit the binding of radioactively labeled to Duffy positive erythrocytes. Preincubation of erythrocytes with anti-Fy6 inhibited the binding of IL-8 in a dosedependent manner, with 70% inhibition at an antibody concentration of 3 nM (Fig.…”

Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people

“…vivax readily infects erythrocytes of the squirrel monkey (Saimiri boliviensis) (29,30). Whereas squirrel monkeys express an Fy6-positive Duffy antigen (29-31), the P. vivax DBP binds poorly, if at all, to squirrel monkey erythrocytes (32), suggesting a PvDBPindependent invasion mechanism.…”