Influenza A virus nucleoprotein peptide–major histocompatibility complex (IAV NP-pMHC)

The Influenza A virus nucleoprotein (NP) peptide–MHC complex is a molecular assembly consisting of a conserved viral peptide fragment bound to a Major Histocompatibility Complex (MHC) molecule, typically Class I, on the surface of infected cells [1, 2]. NP is an internal structural protein essential for viral RNA encapsulation and replication, and it remains highly conserved across various influenza A subtypes, including H1N1 and H5N1 [1, 4]. These complexes serve as the primary signal for the cellular immune system, where they are recognized by specific T-cell receptors (TCRs) on CD8+ cytotoxic T-lymphocytes [2, 3]. This recognition triggers the release of perforins and granzymes, leading to the apoptosis of the infected cell and the secretion of antiviral cytokines like interferon-gamma [3, 5]. Because of the high conservation of NP, these pMHC complexes are major targets for the development of universal influenza vaccines and TCR-engineered T-cell (TCR-T) therapies aimed at providing broad protection against drifting seasonal and pandemic strains [4, 6]. Therapeutic approaches focus on enhancing the recognition of these complexes to bypass the limitations of antibody-mediated immunity, which is often circumvented by viral surface mutations [5, 6].

Other names

NP-pMHC complexInfluenza NP-HLA complexIAV NP-derived epitopeNucleoprotein-MHC class I complexNP380-388/HLA-B*27:05NP338-346/HLA-A*02:01

Recognition of the NP-pMHC complex by specific T-cell receptors (TCRs) triggers CD8+ cytotoxic T-lymphocyte (CTL) activation, leading to the lysis of virus-infected cells and the secretion of pro-inflammatory cytokines like IFN-gamma [2, 3, 5].