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

Pathogen-derived peptide antigens presented on Major Histocompatibility Complex (MHC) molecules, collectively known as pMHC complexes, serve as the primary signal for T-cell recognition and activation (Murphy et al., 2016). These complexes are formed when intracellular or extracellular pathogen proteins are proteolytically processed into short peptides and loaded onto MHC Class I or Class II molecules for display on the cell surface (Rossjohn et al., 2015). MHC Class I-peptide complexes are recognized by CD8+ T cells, leading to the direct lysis of infected cells, while MHC Class II-peptide complexes are recognized by CD4+ T cells to coordinate broader immune responses (Janeway et al., 2001). In drug development, pMHC complexes are the targets of various immunotherapies, including vaccines that aim to prime the immune system and TCR-engineered T-cell (TCR-T) therapies designed to recognize specific viral or bacterial epitopes (Heemskerk et al., 2007). The specificity of the TCR-pMHC interaction is crucial for avoiding autoimmunity, as cross-reactivity with self-peptides can lead to off-target tissue damage (Akatsuka, 2020). Furthermore, the high diversity of HLA alleles in the human population necessitates personalized or HLA-specific approaches for therapies targeting these complexes (European Medicines Agency, 2022).

Other names

pMHCPeptide-MHC complexHLA-peptide complexAntigen-MHC complexMHC-peptide complex

Recognition by T-cell receptors (TCRs) on CD8+ or CD4+ T cells, triggering intracellular signaling cascades that lead to T-cell proliferation, cytokine production, and cytotoxic activity against the presenting cell (Rossjohn et al., 2015).