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Vaccination with altered peptide ligands of a Plasmodium berghei circumsporozoite protein CD8 T-cell epitope: A model to generate T cells resistant to immune interference by polymorphic epitopes

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Minigo, G, Flanagan, KL, Slattery, RM and Plebanski, M 2017 , 'Vaccination with altered peptide ligands of a Plasmodium berghei circumsporozoite protein CD8 T-cell epitope: A model to generate T cells resistant to immune interference by polymorphic epitopes' , Frontiers in Immunology, vol. 8 , pp. 1-9 , doi: 10.3389/fimmu.2017.00115.

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Abstract

Many pathogens, including the malaria parasite Plasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell epitope from the circumsporozoite protein (CS) of Plasmodium berghei (SYIPSAEKI), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive altered peptide ligand (APL) epitopes (SYIPSAEDI or SYIPSAEAI) has radically different effects on immunity. Hence, co-immunization or sequential stimulation in vivo of SYIPSAEKI with its APL antagonist SYIPSAEDI decreases immunity to both epitopes. By contrast, co-immunization with SYIPSAEAI has no apparent initial effect, but it renders the immune response to SYIPSAEKI resistant to being turned off by subsequent immunization with SYIPSAEDI. These results suggest a novel strategy for vaccines that target polymorphic epitopes potentially capable of mutual immune interference in the field, by initiating an immune response by co-immunization with the desired index epitope, together with a carefully selected "potentiator" APL peptide.

Item Type: Article
Authors/Creators:Minigo, G and Flanagan, KL and Slattery, RM and Plebanski, M
Keywords: plasmodium, T cell, altered peptide ligand, antagonism, cross-reactivity, dendritic cell; malaria, vaccine
Journal or Publication Title: Frontiers in Immunology
Publisher: Frontiers Research Foundation
ISSN: 1664-3224
DOI / ID Number: 10.3389/fimmu.2017.00115
Copyright Information:

Copyright 2017 Mingo, Flanagan, Slattery and Plebanski. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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