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...
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Public Library of Science (PLoS)
2013-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003303&type=printable |
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| author | Julius Clemence R Hafalla Karolis Bauza Johannes Friesen Gloria Gonzalez-Aseguinolaza Adrian V S Hill Kai Matuschewski |
| author_facet | Julius Clemence R Hafalla Karolis Bauza Johannes Friesen Gloria Gonzalez-Aseguinolaza Adrian V S Hill Kai Matuschewski |
| author_sort | Julius Clemence R Hafalla |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-4d95f7aaadd14d57bfcbed37a7cc86d1 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2013-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-4d95f7aaadd14d57bfcbed37a7cc86d12025-08-20T03:26:48ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-05-0195e100330310.1371/journal.ppat.1003303Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling.Julius Clemence R HafallaKarolis BauzaJohannes FriesenGloria Gonzalez-AseguinolazaAdrian V S HillKai MatuschewskiCD8⁺ 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003303&type=printable |
| spellingShingle | Julius Clemence R Hafalla Karolis Bauza Johannes Friesen Gloria Gonzalez-Aseguinolaza Adrian V S Hill Kai Matuschewski Identification of targets of CD8⁺ T cell responses to malaria liver stages by genome-wide epitope profiling. PLoS Pathogens |
| 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 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003303&type=printable |
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