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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: | 2018-06-07 |
| Downloads: | 3 View Download Statistics |
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