Journal Article

DKFZ-2025-01427

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Epitope and HLA specificity of human TCRs against Plasmodium falciparum circumsporozoite protein.

van Dijk, H. (First author)DKFZ* ; Wahl, I.DKFZ* ; Kraker, S.DKFZ* ; Robben, P. M. ; Dutta, S. ; Wardemann, H. (Last author)DKFZ*

2025
Rockefeller Univ. Press New York, NY

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Please use a persistent id in citations: doi:10.1084/jem.20250044

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.

Keyword(s): Humans (MeSH) ; Plasmodium falciparum: immunology (MeSH) ; Protozoan Proteins: immunology (MeSH) ; Epitopes, T-Lymphocyte: immunology (MeSH) ; Malaria Vaccines: immunology (MeSH) ; CD4-Positive T-Lymphocytes: immunology (MeSH) ; Malaria, Falciparum: immunology (MeSH) ; Malaria, Falciparum: prevention & control (MeSH) ; Receptors, Antigen, T-Cell: immunology (MeSH) ; Receptors, Antigen, T-Cell: genetics (MeSH) ; CD8-Positive T-Lymphocytes: immunology (MeSH) ; HLA Antigens: immunology (MeSH) ; Amino Acid Sequence (MeSH) ; Protozoan Proteins ; circumsporozoite protein, Protozoan ; Epitopes, T-Lymphocyte ; Malaria Vaccines ; Receptors, Antigen, T-Cell ; HLA Antigens

Note: #EA:D130#LA:D130#

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Contributing Institute(s):

1. B-Zell-Immunologie (D130)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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