Home > Publications database > Epitope and HLA specificity of human TCRs against Plasmodium falciparum circumsporozoite protein. > print

001     302887
005     20250720021530.0
024 7 _ |a 10.1084/jem.20250044
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024 7 _ |a 1540-9358
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024 7 _ |a 1540-9538
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037 _ _ |a DKFZ-2025-01427
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a van Dijk, Hannah
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245 _ _ |a Epitope and HLA specificity of human TCRs against Plasmodium falciparum circumsporozoite protein.
260 _ _ |a New York, NY
|c 2025
|b Rockefeller Univ. Press
336 7 _ |a article
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520 _ _ |a 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.
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650 _ 7 |a Protozoan Proteins
|2 NLM Chemicals
650 _ 7 |a circumsporozoite protein, Protozoan
|2 NLM Chemicals
650 _ 7 |a Epitopes, T-Lymphocyte
|2 NLM Chemicals
650 _ 7 |a Malaria Vaccines
|2 NLM Chemicals
650 _ 7 |a Receptors, Antigen, T-Cell
|2 NLM Chemicals
650 _ 7 |a HLA Antigens
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Plasmodium falciparum: immunology
|2 MeSH
650 _ 2 |a Protozoan Proteins: immunology
|2 MeSH
650 _ 2 |a Epitopes, T-Lymphocyte: immunology
|2 MeSH
650 _ 2 |a Malaria Vaccines: immunology
|2 MeSH
650 _ 2 |a CD4-Positive T-Lymphocytes: immunology
|2 MeSH
650 _ 2 |a Malaria, Falciparum: immunology
|2 MeSH
650 _ 2 |a Malaria, Falciparum: prevention & control
|2 MeSH
650 _ 2 |a Receptors, Antigen, T-Cell: immunology
|2 MeSH
650 _ 2 |a Receptors, Antigen, T-Cell: genetics
|2 MeSH
650 _ 2 |a CD8-Positive T-Lymphocytes: immunology
|2 MeSH
650 _ 2 |a HLA Antigens: immunology
|2 MeSH
650 _ 2 |a Amino Acid Sequence
|2 MeSH
700 1 _ |a Wahl, Ilka
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700 1 _ |a Kraker, Sara
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700 1 _ |a Robben, Paul M
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700 1 _ |a Dutta, Sheetij
|0 0000-0002-4571-1880
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700 1 _ |a Wardemann, Hedda
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773 _ _ |a 10.1084/jem.20250044
|g Vol. 222, no. 9, p. e20250044
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