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

✍ Scribed by Edwin A. M. Lee; Katie L. Flanagan; Gabriela Minigo; William H. H. Reece; Robin Bailey; Margaret Pinder; Adrian V. S. Hill; Magdalena Plebanski

• Book ID: 102169586
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 280 KB
• Volume: 36
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200526010

✦ Synopsis

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‐γ 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.