Major histocompatibility complex class I-restricted tumor antigen peptide (MHC-I tumor antigen)

Major histocompatibility complex (MHC) class I-restricted tumor antigen peptides are short amino acid sequences, typically 8 to 11 residues long, that are processed from intracellular proteins and presented on the cell surface by MHC class I molecules (NIH, 2023). These peptides serve as the primary recognition signals for CD8+ cytotoxic T lymphocytes, allowing the immune system to identify and eliminate cells expressing mutated or abnormally expressed proteins (PubMed, 2022). In oncology, these complexes are highly specific targets for advanced immunotherapies, including T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers like Tebentafusp (FDA, 2022). Unlike traditional antibody targets that must be surface proteins, MHC-restricted peptides allow for the targeting of the entire intracellular proteome, significantly expanding the range of druggable cancer targets (Nature Reviews Cancer, 2021). However, therapeutic success depends on the presence of specific HLA alleles and can be hindered by tumor-mediated HLA downregulation or off-target cross-reactivity with similar peptides in healthy tissues (Journal of Clinical Oncology, 2023).

Other names

Tumor-associated antigen (TAA)Tumor-specific antigen (TSA)NeoantigenPeptide-MHC complexpMHCHLA-restricted tumor peptide

Recognition of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-mimetic antibodies, leading to the recruitment and activation of cytotoxic T lymphocytes (CTLs) and subsequent lysis of the target cell (Nature Reviews Drug Discovery, 2022).