Pathogen-derived peptide–Major Histocompatibility Complex (pMHC) (pMHC)

Pathogen-derived peptide–Major Histocompatibility Complex (pMHC) complexes are molecular assemblies formed when host cells process proteins from invading pathogens into short peptide fragments and display them on the cell surface via MHC molecules [4]. These complexes are the primary targets for the adaptive immune system, specifically recognized by the T-cell receptors (TCRs) of CD8+ and CD4+ T cells [1]. In therapeutic contexts, pMHCs are targeted to eliminate cells infected by viruses (such as EBV, HBV, or HIV) or intracellular bacteria that are otherwise hidden from traditional antibody-based therapies [3]. Modern therapeutic strategies include the use of TCR-engineered T cells (TCR-T), allogeneic virus-specific T cells, and TCR-mimetic antibodies that bind the pMHC with high specificity [2, 3]. By targeting these complexes, drugs can induce the selective destruction of infected host cells through the release of cytotoxic granules or the induction of apoptosis [1]. However, the effectiveness of these therapies is often limited by the high degree of HLA polymorphism in the human population, requiring treatments to be tailored to specific HLA alleles [4]. Furthermore, a major safety challenge involves the potential for cross-reactivity with self-peptides that share structural similarities with the pathogen-derived peptide, which can lead to severe autoimmune reactions [3].

Other names

Peptide-MHC complexpMHC complexAntigen-MHC complexHLA-peptide complexPathogen-derived pMHC

Recognition by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies leads to the activation of cytotoxic pathways and the subsequent lysis of the infected host cell [1, 3].