{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T21:39:33Z","timestamp":1784929173950,"version":"3.55.0"},"reference-count":62,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"72","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,6,24]]},"abstract":"<jats:p>\n            T follicular helper (T\n            <jats:sub>FH<\/jats:sub>\n            ) cells play a crucial role in the development of long-lived, high-quality B cell responses after infection and vaccination. However, little is known about how antigen-specific T\n            <jats:sub>FH<\/jats:sub>\n            cells clonally evolve in response to complex pathogens and what guides the targeting of different epitopes. Here, we assessed the cell phenotype, clonal dynamics, and T cell receptor (TCR) specificity of human circulating T\n            <jats:sub>FH<\/jats:sub>\n            (cT\n            <jats:sub>FH<\/jats:sub>\n            ) cells during successive malaria immunizations with radiation-attenuated\n            <jats:italic>Plasmodium falciparum<\/jats:italic>\n            (\n            <jats:italic>Pf<\/jats:italic>\n            ) sporozoites. Repeated parasite exposures induced a dynamic, polyclonal cT\n            <jats:sub>FH<\/jats:sub>\n            response with high frequency of cells specific to a small number of epitopes in\n            <jats:italic>Pf<\/jats:italic>\n            circumsporozoite protein (PfCSP), the primary sporozoite surface protein and well-defined vaccine target. Human leukocyte antigen (HLA) restrictions and differences in TCR generation probability were associated with differences in the epitope targeting frequency and indicated the potential of amino acids 311 to 333 in the Th2R\/T* region as a T cell supertope. But most of vaccine-induced anti\u2013amino acid 311 to 333 TCRs, including convergent TCRs with high sequence similarity, failed to tolerate natural polymorphisms in their target peptide sequence, thus demonstrating that the T\n            <jats:sub>FH<\/jats:sub>\n            cell response was limited to the vaccine strain. These data suggest that the high parasite diversity in endemic areas will limit boosting of the vaccine-induced T\n            <jats:sub>FH<\/jats:sub>\n            cell response by natural infections. Our findings may guide the further design of PfCSP-based malaria vaccines able to induce potent T helper cell responses for broad, long-lasting antibody responses.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.abm9644","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T17:58:21Z","timestamp":1654883901000},"source":"Crossref","is-referenced-by-count":17,"title":["Clonal evolution and TCR specificity of the human T\n            <sub>FH<\/sub>\n            cell response to\n            <i>Plasmodium falciparum<\/i>\n            CSP"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9854-7711","authenticated-orcid":true,"given":"Ilka","family":"Wahl","sequence":"first","affiliation":[{"name":"Division of B Cell Immunology, German Cancer Research Center, Heidelberg, Germany."},{"name":"Biosciences Faculty, University of Heidelberg, Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna S.","family":"Obraztsova","sequence":"additional","affiliation":[{"name":"Division of B Cell Immunology, German Cancer Research Center, Heidelberg, Germany."},{"name":"Biosciences Faculty, University of Heidelberg, Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-3629","authenticated-orcid":true,"given":"Julia","family":"Puchan","sequence":"additional","affiliation":[{"name":"Division of B Cell Immunology, German Cancer Research Center, Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2482-4541","authenticated-orcid":true,"given":"Rebecca","family":"Hundsdorfer","sequence":"additional","affiliation":[{"name":"Division of B Cell Immunology, German Cancer Research Center, Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0426-6418","authenticated-orcid":true,"given":"Sumana","family":"Chakravarty","sequence":"additional","affiliation":[{"name":"Sanaria Inc., Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8598-8905","authenticated-orcid":true,"given":"B. Kim Lee","family":"Sim","sequence":"additional","affiliation":[{"name":"Sanaria Inc., Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-9505","authenticated-orcid":true,"given":"Stephen L.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Sanaria Inc., Rockville, MD 20850, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3926-4113","authenticated-orcid":true,"given":"Peter G.","family":"Kremsner","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine and German Center for Infection Research, University of T\u00fcbingen, T\u00fcbingen, Germany."},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9, Gabon."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Mordm\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine and German Center for Infection Research, University of T\u00fcbingen, T\u00fcbingen, Germany."},{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3921-5933","authenticated-orcid":true,"given":"Hedda","family":"Wardemann","sequence":"additional","affiliation":[{"name":"Division of B Cell Immunology, German Cancer Research Center, Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075032"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055605"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161794"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190301"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.12.016"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.12.012"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.06.002"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1102287"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06957-4"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60721-8"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4512"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aap8029"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4513"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0881-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51889"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.6.1.10396"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1211548"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241800"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202149392"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07327"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.4.1199"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1988.tb03104.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830180422"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2480642"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa379"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/9858"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0289-6"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0464"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aag2152"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.004"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01660"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100157"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100207"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029421"},{"key":"e_1_3_3_36_2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4049\/jimmunol.151.1.489","article-title":"CD4+ T cell clones obtained from Plasmodium falciparum sporozoite-immunized volunteers recognize polymorphic sequences of the circumsporozoite protein","volume":"151","author":"Moreno A.","year":"1993","unstructured":"A. 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