Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming.
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...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1826287688883372032 |
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| author | Lee, E Flanagan, K Minigo, G Reece, W Bailey, R Pinder, M Hill, A Plebanski, M |
| author_facet | Lee, E Flanagan, K Minigo, G Reece, W Bailey, R Pinder, M Hill, A Plebanski, M |
| author_sort | Lee, E |
| collection | OXFORD |
| description | 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-gamma 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. |
| first_indexed | 2024-03-07T02:02:25Z |
| format | Journal article |
| id | oxford-uuid:9dcd44da-9b3e-45a3-b1a2-574868195a49 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:02:25Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:9dcd44da-9b3e-45a3-b1a2-574868195a492022-03-27T00:45:47ZDimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9dcd44da-9b3e-45a3-b1a2-574868195a49EnglishSymplectic Elements at Oxford2006Lee, EFlanagan, KMinigo, GReece, WBailey, RPinder, MHill, APlebanski, MThe 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-gamma 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. |
| spellingShingle | Lee, E Flanagan, K Minigo, G Reece, W Bailey, R Pinder, M Hill, A Plebanski, M Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming. |
| title | Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming. |
| title_full | Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming. |
| title_fullStr | Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming. |
| title_full_unstemmed | Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming. |
| title_short | Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off memory T cells and interfere with T cell priming. |
| title_sort | dimorphic plasmodium falciparum merozoite surface protein 1 epitopes turn off memory t cells and interfere with t cell priming |
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