Human T-cell receptor recognizing Liver Stage Antigen 3 (LSA-3) (TCR-LSA3)

Human T-cell receptors (TCRs) recognizing Liver Stage Antigen 3 (LSA-3) are critical components of the adaptive immune response against Plasmodium falciparum, the primary causative agent of malaria (Daubersies et al., 2000, Nat. Med.). LSA-3 is a large, highly conserved protein expressed during the pre-erythrocytic stages of the parasite's life cycle, specifically in sporozoites and infected hepatocytes (Bottius et al., 1996, J. Immunol.). These TCRs are found on both CD4+ and CD8+ T cells and recognize specific LSA-3-derived peptides presented by HLA Class II and Class I molecules, respectively (Perlaza et al., 2001, Eur. J. Immunol.). Upon recognition, these T cells orchestrate an immune response characterized by the production of interferon-gamma (IFN-gamma) and the direct lysis of infected liver cells, thereby preventing the transition of the parasite to the symptomatic blood stage. Because LSA-3 is consistently expressed across different parasite strains and induces strong cellular immunity, it has been a primary target for vaccine development, such as the LSA3-729 candidate (Hill, 2011, Nat. Rev. Immunol.). Therapeutic strategies focus on using LSA-3-derived peptides or recombinant proteins to expand the population of T cells bearing these specific TCRs. However, the high degree of HLA polymorphism in human populations presents a challenge for universal vaccine design, as different HLA alleles present different LSA-3 epitopes.

Other names

LSA-3-specific T-cell receptorT-cell receptor recognizing Plasmodium falciparum LSA-3LSA-3 TCRT-cell receptor recognizing LSA-3-derived peptides

Activation of antigen-specific T cells through TCR binding to LSA-3 peptide-MHC complexes, leading to the elimination of Plasmodium falciparum liver-stage parasites.