Human T-cell receptor specific for Enterovirus A71 peptide–MHC complex (EV-A71-specific TCR)

Human T-cell receptors (TCRs) specific for Enterovirus A71 (EV-A71) peptide–MHC complexes are specialized immune receptors that recognize viral antigens presented on the surface of infected cells (Tan et al., 2019, Journal of Virology). These TCRs typically target epitopes derived from the EV-A71 capsid proteins, such as VP1, when they are bound to specific Human Leukocyte Antigen (HLA) molecules like HLA-A*02:01 (Li et al., 2012, Journal of Infectious Diseases). The interaction between the TCR and the peptide-MHC (pMHC) complex is the primary event that triggers CD8+ cytotoxic T-cell activation, leading to the secretion of pro-inflammatory cytokines and the lysis of the virus-harboring cell. EV-A71 is a major cause of hand, foot, and mouth disease (HFMD) and is associated with severe, sometimes fatal, neurological complications in young children (Ye et al., 2020, Frontiers in Immunology). Because natural immunity can be insufficient in severe cases, these TCRs are being investigated as the basis for TCR-engineered T-cell (TCR-T) therapies, which involve modifying a patient's T cells to express these specific receptors. This therapeutic approach aims to provide a potent, targeted immune response to clear the viral infection more effectively than the endogenous immune system. However, the clinical application of EV-A71-specific TCRs faces challenges such as the risk of off-target cross-reactivity with self-peptides and the potential for inducing systemic inflammatory responses.

Other names

EV-A71-specific T-cell receptorEnterovirus 71-specific TCRTCR specific for EV-A71 pMHCEV-A71 VP1-specific T-cell receptor

The TCR specifically binds to EV-A71-derived peptides (e.g., from the VP1 protein) presented by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01, on the surface of infected cells. This binding event triggers a signaling cascade through the CD3 complex, leading to T-cell proliferation, the release of cytotoxic granules (perforin and granzymes), and the secretion of pro-inflammatory cytokines like IFN-gamma to eliminate the virus.