Antigen-Major Histocompatibility Complex (pMHC)

Antigen-Major Histocompatibility Complex (pMHC) complexes are essential molecular assemblies consisting of a peptide fragment bound within the groove of a Major Histocompatibility Complex (MHC) molecule, referred to as Human Leukocyte Antigen (HLA) in humans. Their primary biological function is to present intracellular or extracellular antigens to T-cell receptors (TCRs), a process fundamental to adaptive immune surveillance and the initiation of T-cell-mediated immune responses (Janeway's Immunobiology, 9th Ed, 2016). MHC Class I molecules typically present endogenous peptides to CD8+ cytotoxic T cells, while MHC Class II molecules present exogenous peptides to CD4+ helper T cells (Nature Reviews Immunology, 2016). In oncology, pMHC complexes presenting tumor-associated antigens (TAAs) or neoantigens are primary targets for immunotherapy, as they allow the immune system to recognize internal cellular mutations that are not accessible to traditional antibodies (Frontiers in Immunology, 2020). Therapeutic interventions targeting pMHC include TCR-engineered T cells (TCR-T) and bispecific T-cell engagers like Tebentafusp, which specifically recognizes the gp100 peptide presented by HLA-A*02:01 (New England Journal of Medicine, 2021). However, targeting these complexes poses significant challenges, including the risk of off-target cross-reactivity with similar peptides in healthy tissues and the potential for tumor escape through HLA downregulation or loss of heterozygosity (Journal for ImmunoTherapy of Cancer, 2019).

Other names

Peptide-MHC complexpMHCHLA-peptide complexMHC-peptide complexp/MHCAntigen-HLA complex

T-cell receptor (TCR) mimicry and redirection of T-cell cytotoxicity toward cells presenting specific intracellular antigens.