HLA-A*02:01-restricted tumor-associated antigen peptide-MHC complex (HLA-A2/TAA pMHC)

The HLA-A*02:01-restricted tumor-associated antigen (TAA) peptide-MHC complex is a fundamental target in cancer immunotherapy, representing the mechanism by which the immune system identifies intracellular oncogenic proteins (Restifo et al., 2012). HLA-A2, a common MHC class I allele, presents 8-11 amino acid peptides derived from TAAs—such as NY-ESO-1, gp100, or MAGE-A4—on the cell surface (Gonzalez-Galarza et al., 2020). These complexes are recognized by specific CD8+ T-cell receptors (TCRs), which initiate a cytotoxic response against the presenting cell (Rossjohn et al., 2015). Modern therapies like TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers like Tebentafusp are designed to bind these specific pMHC complexes with high affinity to eradicate tumors (Nathan et al., 2021). However, the high similarity between certain TAAs and self-peptides poses a risk of off-target toxicity, where healthy tissues are inadvertently attacked (Linette et al., 2013). Furthermore, tumor evolution often leads to the loss of HLA expression or antigen processing components, resulting in immune evasion and therapeutic resistance (Garrido et al., 2016).

Other names

HLA-A2-restricted peptide-MHC complexpMHC complexHLA-A2/peptide complexMHC class I-restricted tumor antigenT-cell receptor-ligand complex

Therapeutic agents such as TCR-engineered T-cells or bispecific T-cell engagers bind specifically to the peptide-HLA-A*02:01 complex on the cell surface, triggering T-cell activation, cytokine release, and direct lysis of the target cell.