{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:03:11Z","timestamp":1785402191705,"version":"3.56.0"},"reference-count":64,"publisher":"Rockefeller University Press","issue":"9","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008658","name":"Deutsches Krebsforschungszentrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008658","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:p>Plasmodium 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.<\/jats:p>","DOI":"10.1084\/jem.20250044","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T02:20:44Z","timestamp":1750299644000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Epitope and HLA specificity of human TCRs against\n                    <i>Plasmodium falciparum<\/i>\n                    circumsporozoite protein"],"prefix":"10.1084","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9712-8371","authenticated-orcid":true,"given":"Hannah","family":"van Dijk","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cdgtt98","id-type":"ROR","asserted-by":"publisher"}],"name":"B Cell Immunology, German Cancer Research Center 1 , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9854-7711","authenticated-orcid":true,"given":"Ilka","family":"Wahl","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cdgtt98","id-type":"ROR","asserted-by":"publisher"}],"name":"B Cell Immunology, German Cancer Research Center 1 , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4617-1975","authenticated-orcid":true,"given":"Sara","family":"Kraker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cdgtt98","id-type":"ROR","asserted-by":"publisher"}],"name":"B Cell Immunology, German Cancer Research Center 1 , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0747-6872","authenticated-orcid":true,"given":"Paul M.","family":"Robben","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0145znz58","id-type":"ROR","asserted-by":"publisher"}],"name":"Biologics Research and Development Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research 2 , Silver Spring, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4571-1880","authenticated-orcid":true,"given":"Sheetij","family":"Dutta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0145znz58","id-type":"ROR","asserted-by":"publisher"}],"name":"Biologics Research and Development Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research 2 , Silver Spring, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3921-5933","authenticated-orcid":true,"given":"Hedda","family":"Wardemann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cdgtt98","id-type":"ROR","asserted-by":"publisher"}],"name":"B Cell Immunology, German Cancer Research Center 1 , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"2025071009493199300_bib1","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1056\/NEJMoa1102287","article-title":"First results of phase 3 trial of RTS,S\/AS01 malaria vaccine in African children","volume":"365","author":"Agnandji","year":"2011","journal-title":"N. 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