Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata
Although parasite strain-restricted CD8 T cell responses have been described for several protozoa, the precise role of antigenic variability in immunity is poorly understood. The tick-borne protozoan parasiteTheileria annulatainfects leukocytes and causes an acute, often fatal lymphoproliferative di...
| Autores principales: | , , , , , , , , |
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| Formato: | Journal Article |
| Lenguaje: | Inglés |
| Publicado: |
American Society for Microbiology
2011
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| Materias: | |
| Acceso en línea: | https://hdl.handle.net/10568/129596 |
| _version_ | 1855525984596393984 |
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| author | MacHugh, Niall D. Weir, William Burrells, Alison Lizundia, Regina Graham, Simon P. Taracha, Evans L. Shiels, Brian R. Langsley, Gordon Morrison, W. Ivan |
| author_browse | Burrells, Alison Graham, Simon P. Langsley, Gordon Lizundia, Regina MacHugh, Niall D. Morrison, W. Ivan Shiels, Brian R. Taracha, Evans L. Weir, William |
| author_facet | MacHugh, Niall D. Weir, William Burrells, Alison Lizundia, Regina Graham, Simon P. Taracha, Evans L. Shiels, Brian R. Langsley, Gordon Morrison, W. Ivan |
| author_sort | MacHugh, Niall D. |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | Although parasite strain-restricted CD8 T cell responses have been described for several protozoa, the precise role of antigenic variability in immunity is poorly understood. The tick-borne protozoan parasiteTheileria annulatainfects leukocytes and causes an acute, often fatal lymphoproliferative disease in cattle. Building on previous evidence of strain-restricted CD8 T cell responses toT. annulata, this study set out to identify and characterize the variability of the target antigens. Three antigens were identified by screening expressed parasite cDNAs with specific CD8 T cell lines. In cattle expressing the A10 class I major histocompatibility complex haplotype, A10-restricted CD8 T cell responses were shown to be focused entirely on a single dominant epitope in one of these antigens (Ta9). Sequencing of the Ta9 gene from field isolates ofT. annulatademonstrated extensive sequence divergence, resulting in amino acid polymorphism within the A10-restricted epitope and a second A14-restricted epitope. Statistical analysis of the allelic sequences revealed evidence of positive selection for amino acid substitutions within the region encoding the CD8 T cell epitopes. Sequence differences in the A10-restricted epitope were shown to result in differential recognition by individual CD8 T cell clones, while clones also differed in their ability to recognize different alleles. Moreover, the representation of these clonal specificities within the responding CD8 T cell populations differed between animals. As well as providing an explanation for incomplete protection observed after heterologous parasite challenge of vaccinated cattle, these results have important implications for the choice of antigens for the development of novel subunit vaccines. |
| format | Journal Article |
| id | CGSpace129596 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2011 |
| publishDateRange | 2011 |
| publishDateSort | 2011 |
| publisher | American Society for Microbiology |
| publisherStr | American Society for Microbiology |
| record_format | dspace |
| spelling | CGSpace1295962025-12-08T09:54:28Z Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata MacHugh, Niall D. Weir, William Burrells, Alison Lizundia, Regina Graham, Simon P. Taracha, Evans L. Shiels, Brian R. Langsley, Gordon Morrison, W. Ivan selection theileria polymorphism cells theileria annulata bovine Although parasite strain-restricted CD8 T cell responses have been described for several protozoa, the precise role of antigenic variability in immunity is poorly understood. The tick-borne protozoan parasiteTheileria annulatainfects leukocytes and causes an acute, often fatal lymphoproliferative disease in cattle. Building on previous evidence of strain-restricted CD8 T cell responses toT. annulata, this study set out to identify and characterize the variability of the target antigens. Three antigens were identified by screening expressed parasite cDNAs with specific CD8 T cell lines. In cattle expressing the A10 class I major histocompatibility complex haplotype, A10-restricted CD8 T cell responses were shown to be focused entirely on a single dominant epitope in one of these antigens (Ta9). Sequencing of the Ta9 gene from field isolates ofT. annulatademonstrated extensive sequence divergence, resulting in amino acid polymorphism within the A10-restricted epitope and a second A14-restricted epitope. Statistical analysis of the allelic sequences revealed evidence of positive selection for amino acid substitutions within the region encoding the CD8 T cell epitopes. Sequence differences in the A10-restricted epitope were shown to result in differential recognition by individual CD8 T cell clones, while clones also differed in their ability to recognize different alleles. Moreover, the representation of these clonal specificities within the responding CD8 T cell populations differed between animals. As well as providing an explanation for incomplete protection observed after heterologous parasite challenge of vaccinated cattle, these results have important implications for the choice of antigens for the development of novel subunit vaccines. 2011-05 2023-03-10T14:40:48Z 2023-03-10T14:40:48Z Journal Article https://hdl.handle.net/10568/129596 en Open Access American Society for Microbiology MacHugh, Niall D.; Weir, William; Burrells, Alison; Lizundia, Regina; Graham, Simon P.; Taracha, Evans L.; Shiels, Brian R.; Langsley, Gordon; Morrison, W. Ivan. 2011. Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata. Infection and Immunity 79: 2059-2069 |
| spellingShingle | selection theileria polymorphism cells theileria annulata bovine MacHugh, Niall D. Weir, William Burrells, Alison Lizundia, Regina Graham, Simon P. Taracha, Evans L. Shiels, Brian R. Langsley, Gordon Morrison, W. Ivan Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata |
| title | Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata |
| title_full | Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata |
| title_fullStr | Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata |
| title_full_unstemmed | Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata |
| title_short | Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata |
| title_sort | extensive polymorphism and evidence of immune selection in a highly dominant antigen recognized by bovine cd8 t cells specific for theileria annulata |
| topic | selection theileria polymorphism cells theileria annulata bovine |
| url | https://hdl.handle.net/10568/129596 |
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