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000302887 041__ $$aEnglish
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000302887 1001_ $$0P:(DE-He78)d1a0283ba844508b48375260b19231fa$$avan Dijk, Hannah$$b0$$eFirst author$$udkfz
000302887 245__ $$aEpitope and HLA specificity of human TCRs against Plasmodium falciparum circumsporozoite protein.
000302887 260__ $$aNew York, NY$$bRockefeller Univ. Press$$c2025
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000302887 520__ $$aPlasmodium falciparum malaria remains a significant global health challenge. Current vaccines elicit antibody responses against circumsporozoite protein (PfCSP) that prevent the infection of hepatocytes but offer only moderate protection. Cellular immunity has emerged as a critical component of preerythrocytic protection that might be leveraged to develop improved PfCSP vaccines. Here, we characterized the clonality, molecular features, epitope specificity, and HLA restrictions of the human PfCSP-specific CD4+ and CD8+ T cell response to vaccination with an adjuvanted PfCSP vaccine, FMP013/ALFQ. Using TCR expression cloning, we identified novel conserved CD4+ T cell epitopes in the PfCSP N terminus and showed that the C-terminal CS.T3 epitope was targeted by CD4+ and rare CD8+ T cells, which recognized this epitope co-receptor independently presented on a class II HLA. Our findings provide insights into the utility of these epitopes as targets for strain-transcending immunity compared with the immunodominant but highly polymorphic epitopes in the PfCSP C terminus, offering guidance for the design of improved malaria vaccines.
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000302887 650_7 $$2NLM Chemicals$$aProtozoan Proteins
000302887 650_7 $$2NLM Chemicals$$acircumsporozoite protein, Protozoan
000302887 650_7 $$2NLM Chemicals$$aEpitopes, T-Lymphocyte
000302887 650_7 $$2NLM Chemicals$$aMalaria Vaccines
000302887 650_7 $$2NLM Chemicals$$aReceptors, Antigen, T-Cell
000302887 650_7 $$2NLM Chemicals$$aHLA Antigens
000302887 650_2 $$2MeSH$$aHumans
000302887 650_2 $$2MeSH$$aPlasmodium falciparum: immunology
000302887 650_2 $$2MeSH$$aProtozoan Proteins: immunology
000302887 650_2 $$2MeSH$$aEpitopes, T-Lymphocyte: immunology
000302887 650_2 $$2MeSH$$aMalaria Vaccines: immunology
000302887 650_2 $$2MeSH$$aCD4-Positive T-Lymphocytes: immunology
000302887 650_2 $$2MeSH$$aMalaria, Falciparum: immunology
000302887 650_2 $$2MeSH$$aMalaria, Falciparum: prevention & control
000302887 650_2 $$2MeSH$$aReceptors, Antigen, T-Cell: immunology
000302887 650_2 $$2MeSH$$aReceptors, Antigen, T-Cell: genetics
000302887 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: immunology
000302887 650_2 $$2MeSH$$aHLA Antigens: immunology
000302887 650_2 $$2MeSH$$aAmino Acid Sequence
000302887 7001_ $$0P:(DE-He78)3f447334d7fc0751e1c3c9c0bdb28c2f$$aWahl, Ilka$$b1$$udkfz
000302887 7001_ $$0P:(DE-He78)78f7283c88ca04cc9f40e50e0030b592$$aKraker, Sara$$b2
000302887 7001_ $$00000-0003-0747-6872$$aRobben, Paul M$$b3
000302887 7001_ $$00000-0002-4571-1880$$aDutta, Sheetij$$b4
000302887 7001_ $$0P:(DE-He78)03b354519d912a2724af6b7c9106d1f5$$aWardemann, Hedda$$b5$$eLast author$$udkfz
000302887 773__ $$0PERI:(DE-600)1477240-1$$a10.1084/jem.20250044$$gVol. 222, no. 9, p. e20250044$$n9$$pe20250044$$tJournal of experimental medicine$$v222$$x0022-1007$$y2025
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