Pathogen-derived peptide-Major Histocompatibility Complex (pMHC)

Pathogen-derived T-cell antigens presented via human Major Histocompatibility Complex (MHC) are the fundamental units of recognition for the adaptive immune system. These targets consist of short peptides derived from viral, bacterial, or other pathogenic proteins that are processed and displayed on the cell surface by MHC molecules, also known as Human Leukocyte Antigens (HLA) (Murphy & Weaver, 2016). The resulting peptide-MHC (pMHC) complex is recognized by the T-cell receptor (TCR), which triggers a cascade of signaling events leading to the destruction of the infected cell (Neefjes et al., 2011). In drug development, these complexes are targeted by various modalities, including vaccines that induce endogenous T-cell responses and adoptive cell therapies like TCR-engineered T cells (TCR-T) (Tan et al., 2021). These therapies are particularly promising for treating chronic infections such as Hepatitis B and C, as well as pathogen-driven cancers like those caused by Human Papillomavirus (HPV) (Zhao et al., 2021). A major challenge in targeting these antigens is the high degree of HLA polymorphism among the human population, requiring treatments to be tailored to specific HLA alleles (Linette et al., 2013). Additionally, the risk of cross-reactivity with similar self-peptides necessitates rigorous screening to avoid autoimmune-like toxicities.

Other names

HLA-peptide complexMHC-restricted pathogen antigenT-cell epitope-MHC complexPathogen-derived pMHCAntigen-presenting MHC complex

Recognition of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-like molecules to trigger targeted cell lysis or immune activation.