Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming

European Journal of Immunology
E A LeeMagdalena Plebanski

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.

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Citations

Mar 3, 2011·Immunologic Research·Lindsay J Edwards, Brian D Evavold
Aug 1, 2008·Transboundary and Emerging Diseases·A P Arez, V E do Rosário
Jan 16, 2007·Clinical Microbiology Reviews·David J Conway
Sep 6, 2007·Infection and Immunity·Ipsita Pal-BhowmickGotam K Jarori
Jun 6, 2009·Current Opinion in Immunology·Sofia Casares, Thomas L Richie
Sep 8, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Fouzia Farooq, Elke S Bergmann-Leitner
Jan 8, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sean C EliasSimon J Draper
Mar 29, 2011·European Journal of Immunology·Matthew Lewis
Feb 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Indu MalhotraChristopher L King
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Oct 19, 2006·International Journal for Parasitology·Gareth D WeedallDavid J Conway
Feb 13, 2008·Accounts of Chemical Research·Manuel E Patarroyo, Manuel A Patarroyo

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