T-cell receptor recognizing Yersinia pestis F1 and V antigens (F1/V-specific TCR)

T-cell receptors (TCRs) recognizing F1- and V-derived peptides presented on MHC class II are specialized immune receptors that play a pivotal role in the defense against Yersinia pestis, the causative agent of plague [1]. The F1 (Caf1) and V (LcrV) antigens are critical virulence factors; F1 forms a protective capsule, while V is essential for the injection of effector proteins into host cells via the type III secretion system [2]. These TCRs are expressed on the surface of CD4+ T lymphocytes and are responsible for identifying specific bacterial peptide fragments displayed by Major Histocompatibility Complex (MHC) class II molecules on antigen-presenting cells [3]. Upon recognition, the TCR initiates a signaling cascade that leads to T-cell activation, proliferation, and the secretion of pro-inflammatory cytokines like interferon-gamma (IFN-γ), which are necessary for activating macrophages to kill the intracellular bacteria [4]. Because of their central role in protective immunity, these TCR-peptide-MHC interactions are the primary focus of subunit vaccine development, such as the rF1-V fusion protein vaccine, which aims to elicit a robust and memory-capable T-cell response [5]. A significant challenge in targeting these receptors is the high degree of MHC polymorphism in human populations, which can lead to variable recognition of specific F1 and V epitopes across different individuals [6].

Other names

F1-specific T-cell receptorV-antigen specific T-cell receptorLcrV-specific TCRCaf1-specific TCRYersinia pestis antigen-specific T-cell receptor

Vaccines containing F1 and V antigens prime the immune system to generate a population of CD4+ T cells expressing these specific TCRs; upon subsequent infection, these TCRs recognize the peptide-MHC II complexes on antigen-presenting cells, triggering a rapid Th1-mediated immune response and macrophage activation to clear Yersinia pestis.