HLA-A*02:01-presented NY-ESO-1 (157-165V) peptide complex (HLA-A2/NY-ESO-1 (157-165V))

The HLA-A*02:01-presented NY-ESO-1 (157-165V) peptide complex is a specific human leukocyte antigen (MHC Class I) structure that displays a fragment of the New York Esophageal Squamous Cell Carcinoma 1 (NY-ESO-1) protein (UniProt P78358). NY-ESO-1 is a prominent cancer-testis antigen (CTA) that is highly expressed in various tumors but restricted to the testis in healthy adults, making it an ideal target for immunotherapy (Chen et al., 2000, J Exp Med 192:737-744). The 157-165V variant (SLLMWITQV) is a modified heteroclitic peptide where the terminal cysteine is replaced by valine to enhance binding stability to the HLA-A*02:01 molecule (UniProt P01892). This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells, triggering an immune response against the presenting cell. Therapeutic interventions, such as TCR-engineered T-cell (TCR-T) therapies like letetresgene autoleucel, are designed to exploit this recognition to eliminate NY-ESO-1-positive cancer cells (D'Angelo et al., 2018, Cancer Discov 8:944-957). Clinical development has focused on treating solid tumors, including synovial sarcoma and melanoma, where NY-ESO-1 expression is prevalent. Monitoring for HLA-A*02:01 status and NY-ESO-1 expression is essential for patient selection in these targeted therapies.

Other names

SLLMWITQV-HLA-A*02:01 complexNY-ESO-1 p157-165 (V9) HLA-A2 complexCTAG1B-HLA-A*02:01 complexNY-ESO-1 (157-165V) pMHC

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and targeted cell lysis.