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

Minigo, G, Flanagan, K, Slattery, R 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, 115, pp. 1-9.


Document type: Journal Article
Collection: Journal Articles

Title 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
Author(s) Minigo, G
Flanagan, K
Slattery, R
Plebanski, M
Year 2017
Journal name Frontiers in Immunology
Volume number 8
Article Number 115
Start page 1
End page 9
Total pages 9
Publisher Frontiers Research Foundation
Abstract © 2017 Minigo, Flanagan, Slattery and Plebanski. 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 offby 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.
Subject Immunology not elsewhere classified
Keyword(s) Altered peptide ligand
Antagonism
Cross-reactivity
Dendritic cell
Malaria
Plasmodium
T cell
Vaccine
DOI - identifier 10.3389/fimmu.2017.00115
Copyright notice Copyright © 2017 Minigo, Flanagan, Slattery and Plebanski. Creative Commons Attribution License (CC BY)
ISSN 1664-3224
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