T-cell receptor recognizing Plasmodium falciparum circumsporozoite protein epitopes (TCR-PfCSP)

The T-cell receptor (TCR) recognizing Plasmodium falciparum circumsporozoite protein (PfCSP) epitopes is a pivotal mediator of the cellular immune response against the pre-erythrocytic stage of malaria. PfCSP is the primary surface protein of sporozoites, and its C-terminal region contains highly conserved and polymorphic T-cell epitopes, such as Th2R and Th3R, which are recognized by CD4+ and CD8+ T cells (Good et al., 1988, Science). CD4+ TCRs interact with PfCSP peptides presented by MHC class II molecules, promoting B-cell maturation and the production of high-affinity antibodies that neutralize sporozoites (RTS,S Clinical Trials Partnership, 2015, Lancet). Simultaneously, CD8+ TCRs recognize PfCSP epitopes on MHC class I molecules of infected hepatocytes, triggering cytotoxic activity to eliminate the parasite reservoir (White et al., 2017, Nature Communications). Therapeutic strategies, primarily vaccines such as RTS,S/AS01 and R21/Matrix-M, are designed to elicit these specific T-cell responses to complement antibody-mediated protection (Datoo et al., 2021, Lancet). The diversity of TCR repertoires and the high degree of genetic polymorphism in PfCSP epitopes present significant challenges for achieving broad-spectrum immunity across different geographic regions (Neafsey et al., 2015, NEJM). Monitoring the activation and frequency of these TCRs serves as a critical biomarker for evaluating vaccine efficacy and the longevity of protective immunity. Understanding the structural basis of TCR-PfCSP-MHC interactions is essential for the rational design of next-generation malaria vaccines.

Other names

PfCSP-specific T-cell receptorCircumsporozoite protein-specific TCRMalaria-specific T-cell receptorCD4+ and CD8+ TCR recognizing PfCSP

Vaccine-induced priming and activation of T-cell receptors to recognize PfCSP-derived peptides presented by Major Histocompatibility Complex (MHC) molecules, leading to CD4+ helper functions and CD8+ cytotoxic elimination of infected hepatocytes.