Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling.
CD8⁺ T cells mediate immunity against Plasmodium liver stages. However, the paucity of parasite-specific epitopes of CD8⁺ T cells has limited our current understanding of the mechanisms influencing the generation, maintenance and efficiency of these responses. To identify antigenic epitopes in a str...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2013
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| _version_ | 1826271133428613120 |
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| author | Hafalla, J Bauza, K Friesen, J Gonzalez-Aseguinolaza, G Hill, A Matuschewski, K Hill, A |
| author_facet | Hafalla, J Bauza, K Friesen, J Gonzalez-Aseguinolaza, G Hill, A Matuschewski, K Hill, A |
| author_sort | Hafalla, J |
| collection | OXFORD |
| description | CD8⁺ T cells mediate immunity against Plasmodium liver stages. However, the paucity of parasite-specific epitopes of CD8⁺ T cells has limited our current understanding of the mechanisms influencing the generation, maintenance and efficiency of these responses. To identify antigenic epitopes in a stringent murine malaria immunisation model, we performed a systematic profiling of H(2b)-restricted peptides predicted from genome-wide analysis. We describe the identification of Plasmodium berghei (Pb) sporozoite-specific gene 20 (S20)- and thrombospondin-related adhesive protein (TRAP)-derived peptides, termed PbS20₃₁₈ and PbTRAP₁₃₀ respectively, as targets of CD8⁺ T cells from C57BL/6 mice vaccinated by whole parasite strategies known to protect against sporozoite challenge. While both PbS20₃₁₈ and PbTRAP₁₃₀ elicit effector and effector memory phenotypes in both the spleens and livers of immunised mice, only PbTRAP₁₃₀-specific CD8⁺ T cells exhibit in vivo cytotoxicity. Moreover, PbTRAP₁₃₀-specific, but not PbS20₃₁₈-specific, CD8⁺ T cells significantly contribute to inhibition of parasite development. Prime/boost vaccination with PbTRAP demonstrates CD8⁺ T cell-dependent efficacy against sporozoite challenge. We conclude that PbTRAP is an immunodominant antigen during liver-stage infection. Together, our results underscore the presence of CD8⁺ T cells with divergent potencies against distinct Plasmodium liver-stage epitopes. Our identification of antigen-specific CD8⁺ T cells will allow interrogation of the development of immune responses against malaria liver stages. |
| first_indexed | 2024-03-06T21:51:50Z |
| format | Journal article |
| id | oxford-uuid:4b8af258-9f14-40ad-8115-c6d841cafd4d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:51:50Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:4b8af258-9f14-40ad-8115-c6d841cafd4d2022-03-26T15:44:16ZIdentification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4b8af258-9f14-40ad-8115-c6d841cafd4dEnglishSymplectic Elements at OxfordPublic Library of Science2013Hafalla, JBauza, KFriesen, JGonzalez-Aseguinolaza, GHill, AMatuschewski, KHill, ACD8⁺ T cells mediate immunity against Plasmodium liver stages. However, the paucity of parasite-specific epitopes of CD8⁺ T cells has limited our current understanding of the mechanisms influencing the generation, maintenance and efficiency of these responses. To identify antigenic epitopes in a stringent murine malaria immunisation model, we performed a systematic profiling of H(2b)-restricted peptides predicted from genome-wide analysis. We describe the identification of Plasmodium berghei (Pb) sporozoite-specific gene 20 (S20)- and thrombospondin-related adhesive protein (TRAP)-derived peptides, termed PbS20₃₁₈ and PbTRAP₁₃₀ respectively, as targets of CD8⁺ T cells from C57BL/6 mice vaccinated by whole parasite strategies known to protect against sporozoite challenge. While both PbS20₃₁₈ and PbTRAP₁₃₀ elicit effector and effector memory phenotypes in both the spleens and livers of immunised mice, only PbTRAP₁₃₀-specific CD8⁺ T cells exhibit in vivo cytotoxicity. Moreover, PbTRAP₁₃₀-specific, but not PbS20₃₁₈-specific, CD8⁺ T cells significantly contribute to inhibition of parasite development. Prime/boost vaccination with PbTRAP demonstrates CD8⁺ T cell-dependent efficacy against sporozoite challenge. We conclude that PbTRAP is an immunodominant antigen during liver-stage infection. Together, our results underscore the presence of CD8⁺ T cells with divergent potencies against distinct Plasmodium liver-stage epitopes. Our identification of antigen-specific CD8⁺ T cells will allow interrogation of the development of immune responses against malaria liver stages. |
| spellingShingle | Hafalla, J Bauza, K Friesen, J Gonzalez-Aseguinolaza, G Hill, A Matuschewski, K Hill, A Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling. |
| title | Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling. |
| title_full | Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling. |
| title_fullStr | Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling. |
| title_full_unstemmed | Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling. |
| title_short | Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling. |
| title_sort | identification of targets of cd8⁺ t cell responses to malaria liver stages by genome wide epitope profiling |
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