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@ARTICLE{vanDijk:302887,
      author       = {H. van Dijk$^*$ and I. Wahl$^*$ and S. Kraker$^*$ and P. M.
                      Robben and S. Dutta and H. Wardemann$^*$},
      title        = {{E}pitope and {HLA} specificity of human {TCR}s against
                      {P}lasmodium falciparum circumsporozoite protein.},
      journal      = {Journal of experimental medicine},
      volume       = {222},
      number       = {9},
      issn         = {0022-1007},
      address      = {New York, NY},
      publisher    = {Rockefeller Univ. Press},
      reportid     = {DKFZ-2025-01427},
      pages        = {e20250044},
      year         = {2025},
      note         = {#EA:D130#LA:D130#},
      abstract     = {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.},
      keywords     = {Humans / Plasmodium falciparum: immunology / Protozoan
                      Proteins: immunology / Epitopes, T-Lymphocyte: immunology /
                      Malaria Vaccines: immunology / CD4-Positive T-Lymphocytes:
                      immunology / Malaria, Falciparum: immunology / Malaria,
                      Falciparum: prevention $\&$ control / Receptors, Antigen,
                      T-Cell: immunology / Receptors, Antigen, T-Cell: genetics /
                      CD8-Positive T-Lymphocytes: immunology / HLA Antigens:
                      immunology / Amino Acid Sequence / Protozoan Proteins (NLM
                      Chemicals) / circumsporozoite protein, Protozoan (NLM
                      Chemicals) / Epitopes, T-Lymphocyte (NLM Chemicals) /
                      Malaria Vaccines (NLM Chemicals) / Receptors, Antigen,
                      T-Cell (NLM Chemicals) / HLA Antigens (NLM Chemicals)},
      cin          = {D130},
      ddc          = {610},
      cid          = {I:(DE-He78)D130-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40637713},
      pmc          = {pmc:PMC12243953},
      doi          = {10.1084/jem.20250044},
      url          = {https://inrepo02.dkfz.de/record/302887},
}