Influenza A virus matrix protein 1 (M1) peptide-HLA complex (M1-pMHC)

The Influenza A virus matrix protein 1 (M1) peptide-MHC complex is a critical immunological target formed when the highly conserved M1 protein is processed and its fragments, most notably the immunodominant M1 58-66 epitope (GILGFVFTL), are presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02:01 (UniProt P03485, PubMed: 25108119). This complex serves as a primary signal for the host's cellular immune system, allowing CD8+ cytotoxic T lymphocytes (CTLs) to identify and eliminate influenza-infected cells. Because the M1 sequence is remarkably stable across various influenza A subtypes, including H1N1 and H5N1, this pMHC complex is a focal point for the development of universal influenza vaccines and adoptive T-cell therapies (PubMed: 30104373). Therapeutic strategies involve engineering T-cell receptors (TCRs) or soluble TCR-like molecules to specifically bind this complex, thereby bypassing the limitations of traditional antibody-mediated immunity which often fails due to viral antigenic drift (PubMed: 31434705). However, clinical challenges include potential cross-reactivity with similar self-peptides and the risk of cytokine release syndrome during intensive T-cell activation.

Other names

M1 58-66 peptide-HLA-A*02:01 complexInfluenza M1 peptide-MHCGILGFVFTL-HLA-A2 complexIAV M1-pMHCMatrix protein 1 (58-66) HLA-A*02:01

Recognition and binding by engineered or endogenous T-cell receptors (TCRs) on CD8+ T cells, leading to cytotoxic T-lymphocyte (CTL) activation and subsequent lysis of influenza-infected cells.