Antigenic variation of bloodstage malaria parasites

Abstract

An antigen on the surface of erythrocytes infected with mature asexual malaria parasites has been shown to undergo antigenic variation in two malaria species. Plasmodium falciparum-infected erythrocytes from squirrel monkeys express a new antigen that is identified by reactivity with antibody from infected animals in an indirect immunofluorescence assay. Cloned P. knowlesi parasites in rhesus monkeys undergo antigenic variation of an erythrocyte surface antigen as defined by antibody-mediated cell agglutination (the SICA test) and indirect immunofluorescence. This variant antigen is a malarial protein that changes both in size (Mr 185 000-225 000) and antigenicity in cloned parasites derived by antigenic variation in vivo. Antigenic variation on the erythrocyte surface probably contributes to the capacity of malaria parasites to establish chronic infections with multiple recrudescences and to the finding that individuals can be repeatedly reinfected. The fundamental reasons for expression of these highly immunogenic antigens on the erythrocyte membrane remain obscure. Other major questions remain to be explored: the repertoire of variant antigens; the genetic basis of antigenic variation and the structural basis for the antigenic uniqueness of each variant antigen. Some properties of malarial antigenic variation indicate that control of antigenic variation in plasmodia will be quite different to antigenic variation in the African trypanosomes. The host spleen is required both for variant antigen expression and antigenic variation, and variant-specific antibody appears to induce antigenic variation rather than select pre-existing variants.