Publications & Reports

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

Lee EA, Flanagan KL, Minigo G, Reece WH, Bailey R, Pinder M, Hill AV, Plebanski M
Molecular Immunology Group, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

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.

Publication

  • Journal: European Journal of Immunology
  • Published: 01/05/2006
  • Volume: 36
  • Issue: 5
  • Pagination: 1168-1178