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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

Citation

Minigo, G and Flanagan, KL and Slattery, RM and Plebanski, M, 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, 8 Article 115. ISSN 1664-3224 (2017) [Refereed Article]


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Copyright Statement

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/

DOI: doi:10.3389/fimmu.2017.00115

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 Details

Item Type:Refereed Article
Keywords:plasmodium, T cell, altered peptide ligand, antagonism, cross-reactivity, dendritic cell; malaria, vaccine
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Flanagan, KL (Dr Katie Flanagan)
ID Code:126084
Year Published:2017
Deposited By:Medicine (Discipline)
Deposited On:2018-05-22
Last Modified:2018-09-11
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