Fc-fucosylation of Plasmodium falciparum-specific IgG varies with antigen and immunization.

Abstract

IgG-mediated effector functions are modulated by the antibody Fc-region glycan composition, and the absence of core fucose is a strong modifier of NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Most plasma IgG is fully Fc-fucosylated, but antigens displayed on host-derived membranes can selectively induce Fc-afucosylated IgG. These antigens include alloantigens, enveloped virus surface proteins, and PfEMP1, a malaria parasite protein expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs). We determined levels and Fc-fucosylation of IgG specific for several P. falciparum antigens in plasma from children naturally exposed to P. falciparum and from vaccinated adults. IgG specific for PfEMP1 (known to be exposed on the IE surface) and PfGARP, a putative IE surface antigen, were markedly Fc-afucosylated, whereas IgG specific for antigens on parasite membranes (merozoites, gametocytes/gametes, and sporozoites) were fully Fc-fucosylated in most of the children naturally exposed to P. falciparum studied here. Immunization of adults with recombinant proteins (MSP1, Pfs230, and CSP) also consistently induced fully Fc-fucosylated IgG. Children with Fc-afucosylated PfGARP-specific IgG had reduced risk of carrying P. falciparum parasites, independent of levels of PfGARP-specific IgG. These results reinforce the hypothesis that Fc-afucosylation of antigen-specific IgG requires exposure of the antigen on a host membrane (context) and is a function of antigen exposure. Host-specific factors appear to play a minor role in this context.