Peptide-Major Histocompatibility Complex class I (pMHC-I)

The Peptide-Major Histocompatibility Complex class I (pMHC-I) is a molecular assembly found on the surface of all nucleated cells, consisting of a polymorphic heavy chain, a β2-microglobulin light chain, and a short peptide (typically 8-12 amino acids) derived from intracellular proteins [2, 4, 10]. Its primary biological function is to present an immunological snapshot of the cell's internal state to CD8+ cytotoxic T cells, enabling the immune system to distinguish between healthy self-cells and those that are infected or malignant [1, 10, 12]. On antigen-presenting cells, these complexes are essential for the initial priming and activation of the adaptive immune response [12, 14]. In diseases like cancer, pMHC-I complexes display neoantigens or overexpressed tumor-associated antigens, making them highly specific targets for immunotherapy [2, 4, 8, 19]. Therapeutic strategies include TCR-engineered T cells (TCR-T), TCR-like antibodies, and bispecific T-cell engagers that recognize these complexes with high precision [1, 9, 13, 18]. However, challenges such as MHC-I downregulation by tumors and the risk of off-target cross-reactivity with similar self-peptides remain significant hurdles in drug development [1, 8, 10, 19].

Other names

HLA-peptide complexAntigen-MHC class I complexpMHC class IMHC-I ligandomepMHC-I complex

Engineered recognition of specific peptide-HLA complexes by TCRs or TCR-like antibodies, leading to T-cell mediated cytotoxicity against the target cell.