title: Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming.
abstract: The leading blood-stage malaria vaccine candidate antigen, Plasmodium falciparum merozoite surface protein-1 (MSP-1) occurs in two major allelic types worldwide. The molecular basis promoting this stable dimorphism is unknown. In this study, we have shown that allelic altered peptide ligand (APL) T cell epitopes of MSP-1 mutually inhibited IFN-gamma secretion as well as proliferation of CD4+ T cells in 27/34 malaria exposed Gambian volunteers. Besides this inhibition of malaria-specific immunity, the same variant epitopes were also able to impair the priming of human T cells in malaria naive individuals. Epitope variants capable of interfering with T cell priming as well as inhibiting memory T cell effector functions offer a uniquely potent combination for immune evasion. Indeed, enhanced co-habitation of parasites bearing such antagonistic allelic epitope regions was observed in a study of 321 West African children, indicating a survival advantage for parasites able to engage this inhibitory immune interference mechanism.
authors.affiliation: Molecular Immunology Group, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Edwin A M
authors.initials: EA
authors.lastname: Lee
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.forename: Gabriela
authors.initials: G
authors.lastname: Minigo
authors.forename: William H H
authors.initials: WH
authors.lastname: Reece
authors.forename: Robin
authors.initials: R
authors.lastname: Bailey
authors.forename: Margaret
authors.initials: M
authors.lastname: Pinder
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D007371:Interferon-gamma