TY  - JOUR
AU  - van Dijk, Hannah
AU  - Wahl, Ilka
AU  - Kraker, Sara
AU  - Robben, Paul M
AU  - Dutta, Sheetij
AU  - Wardemann, Hedda
TI  - Epitope and HLA specificity of human TCRs against Plasmodium falciparum circumsporozoite protein.
JO  - Journal of experimental medicine
VL  - 222
IS  - 9
SN  - 0022-1007
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - DKFZ-2025-01427
SP  - e20250044
PY  - 2025
N1  - #EA:D130#LA:D130#
AB  - 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.
KW  - Humans
KW  - Plasmodium falciparum: immunology
KW  - Protozoan Proteins: immunology
KW  - Epitopes, T-Lymphocyte: immunology
KW  - Malaria Vaccines: immunology
KW  - CD4-Positive T-Lymphocytes: immunology
KW  - Malaria, Falciparum: immunology
KW  - Malaria, Falciparum: prevention & control
KW  - Receptors, Antigen, T-Cell: immunology
KW  - Receptors, Antigen, T-Cell: genetics
KW  - CD8-Positive T-Lymphocytes: immunology
KW  - HLA Antigens: immunology
KW  - Amino Acid Sequence
KW  - Protozoan Proteins (NLM Chemicals)
KW  - circumsporozoite protein, Protozoan (NLM Chemicals)
KW  - Epitopes, T-Lymphocyte (NLM Chemicals)
KW  - Malaria Vaccines (NLM Chemicals)
KW  - Receptors, Antigen, T-Cell (NLM Chemicals)
KW  - HLA Antigens (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40637713
C2  - pmc:PMC12243953
DO  - DOI:10.1084/jem.20250044
UR  - https://inrepo02.dkfz.de/record/302887
ER  -