Tumor-associated peptide-major histocompatibility complex class I (pMHC-I)

The tumor-associated peptide-major histocompatibility complex class I (pMHC-I) is a molecular assembly on the surface of nucleated cells that presents intracellularly derived peptides to the immune system (NIH, 2023). In the context of oncology, these complexes display fragments of mutated proteins (neoantigens) or overexpressed proteins (tumor-associated antigens) to CD8+ cytotoxic T lymphocytes (PubMed, 2021). Recognition of the pMHC-I by the T-cell receptor (TCR) is the fundamental step in initiating an adaptive immune response against cancer (Nature, 2022). Therapeutic strategies targeting these complexes include TCR-mimetic antibodies, soluble TCRs like tebentafusp, and peptide-based vaccines designed to enhance the visibility of tumor cells (FDA, 2022). However, tumors often evade detection by downregulating MHC-I expression or through the heterogeneity of peptide presentation, posing significant challenges for drug development (Frontiers, 2023).

Other names

pMHC-IpHLA-IMHC-I-associated peptideMAPTumor-specific peptide-MHC complexNeoantigen-MHC complexHLA-peptide complex

Targeting of specific peptide-HLA complexes via soluble T-cell receptors (ImmTACs), TCR-mimetic antibodies, or engineered T-cells (TCR-T) to induce cytotoxic T-lymphocyte mediated lysis of tumor cells.