T-cell receptor recognizing internal influenza protein peptide-MHC complex (TCR-pMHC (Influenza))

T-cell receptors (TCRs) that recognize peptide-MHC (pMHC) complexes derived from internal influenza proteins are pivotal for heterosubtypic immunity against influenza viruses. While surface proteins like hemagglutinin undergo rapid antigenic drift, internal proteins such as nucleoprotein (NP), matrix protein 1 (M1), and the polymerase complex (PA, PB1, PB2) remain highly conserved across various strains, including seasonal and pandemic variants (Sridhar et al., 2013, Nature Medicine). TCRs on CD8+ and CD4+ T cells recognize specific epitopes from these proteins when presented by Major Histocompatibility Complex (MHC) molecules on the surface of infected cells (Gras et al., 2010, JBC). This recognition triggers the release of cytotoxic granules and cytokines, facilitating the clearance of the virus. Therapeutic approaches focusing on this target aim to develop universal influenza vaccines or adoptive T-cell therapies that provide broad protection by eliciting T-cell responses against these stable internal antigens (Valkenburg et al., 2014, Current Opinion in Virology). However, the high degree of HLA polymorphism in the human population presents a challenge, as specific TCR-pMHC interactions are restricted to individuals with matching HLA alleles. Furthermore, ensuring that the induced T-cell response is robust enough to prevent illness, rather than just reducing severity, remains a key goal in clinical development.

Other names

Influenza-specific T-cell receptorTCR recognizing influenza internal antigenspMHC-TCR complex (Influenza)CD8+ T-cell receptor for influenza conserved epitopes

Induction of T-cell mediated immunity by presenting conserved internal viral peptides to T-cell receptors via MHC molecules, leading to the destruction of infected cells.