Major Histocompatibility Complex (MHC) - Peptide Complex (pMHC)

The Major Histocompatibility Complex (MHC) - Peptide complex is a fundamental molecular assembly required for the adaptive immune system to recognize and respond to specific antigens (Source: Janeway's Immunobiology). MHC molecules, known as Human Leukocyte Antigens (HLA) in humans, capture short peptide fragments derived from intracellular or extracellular proteins and display them on the cell surface for surveillance by T-cell receptors (TCRs) (Source: NIH - MedlinePlus). This presentation is the primary signal for the activation of antigen-specific CD8+ cytotoxic T cells and CD4+ helper T cells, which subsequently coordinate B-lymphocyte responses and antibody production. In modern oncology, these complexes are targeted by neoantigen vaccines and TCR-engineered T-cell therapies (TCR-T) to direct the immune system against tumor-specific mutations (Source: Nature Reviews Drug Discovery). However, the high degree of HLA polymorphism and the risk of lethal cross-reactivity with similar self-peptides in healthy tissues remain significant challenges for drug development and clinical safety (Source: PubMed - PMC7350250).

Other names

HLA-peptide complexAntigen-MHC complexPeptide-HLA complexpMHC complexAntigen-presenting complex

Drugs targeting this complex typically act as vaccines providing the peptide for endogenous presentation, or as engineered receptors (TCR-T, BiTEs) that bind the specific peptide-MHC assembly to trigger T-cell mediated lysis of the target cell.