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

Peptide–Major Histocompatibility Complex class I (pMHC-I) complexes are molecular assemblies found on the surface of almost all nucleated cells, consisting of a polymorphic HLA heavy chain, a beta-2 microglobulin subunit, and a short antigenic peptide (Source: UniProt P01889). In the context of oncology, these complexes present tumor-associated antigens (TAAs) or neoantigens derived from intracellular proteins that are otherwise inaccessible to traditional antibody-based therapies (Source: NIH/NCI). These complexes serve as the primary recognition signal for CD8+ T-cells via their T-cell receptors (TCRs), triggering an adaptive immune response. Therapeutic strategies targeting pMHC-I include TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers, such as tebentafusp, which are designed to bind specific peptide-HLA combinations with high affinity (Source: PubMed 32661153). Because pMHC-I presentation is essential for immunosurveillance, its downregulation is a frequent mechanism of cancer immune evasion and resistance to immunotherapy.

Other names

pMHC complexHLA-peptide complexTumor-associated antigen-MHC complexMHC-I-peptide complexAntigen-presenting complex

Drugs targeting pMHC-I complexes utilize engineered T-cell receptors (TCRs) or TCR-mimic antibodies to recognize specific peptide-HLA combinations, facilitating the recruitment and activation of cytotoxic T-lymphocytes to lyse the target cell (Source: PubMed 35081294).