Human leukocyte antigen A*02:01 presenting TCR gamma alternate reading frame protein (27-35) peptide (HLA-A*02:01-TARP(27-35))

The HLA-A*02:01-TARP (27-35) complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy, particularly in prostate and breast cancers. It consists of the HLA-A*02:01 molecule presenting a 9-amino acid fragment (VLYRYGSFS) derived from the TCR gamma alternate reading frame protein (TARP) (Wolfgang et al., 2000; Epel et al., 2008). TARP is a tumor-associated antigen highly expressed in over 95% of prostate adenocarcinomas and approximately 50% of breast cancers, while showing very limited expression in normal tissues (Friedrich et al., 2007). This pMHC complex is recognized by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, making it a focal point for the development of TCR-engineered T-cell therapies and therapeutic vaccines (Wood et al., 2016). By targeting this specific presentation, therapies aim to induce a potent and selective immune response against malignant cells. The clinical utility of this target is primarily restricted to patients who are HLA-A*02:01 positive and whose tumors express the TARP protein (Ma et al., 2016). Potential safety concerns include off-target cross-reactivity with similar human peptides and the risk of cytokine release syndrome following T-cell activation.

Other names

HLA-A*02:01-TARP complexTARP 27-35/HLA-A*02:01MHC-peptide complex (TARP 27-35)TARP-A2VLYRYGSFS-HLA-A*02:01

The complex acts as a ligand for specific T-cell receptors (TCRs), facilitating the formation of an immunological synapse and subsequent CD8+ T-cell mediated lysis of the target cell.