HLA-A*02:01-NY-ESO-1 (SLLMWITQV) complex (HLA-A*02:01/NY-ESO-1)

The HLA-A*02:01-NY-ESO-1 (SLLMWITQV) complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy (Robbins et al., 2011). It consists of the HLA-A*02:01 molecule presenting a 9-amino acid epitope derived from the cancer-testis antigen NY-ESO-1 (CTAG1B), specifically the 157-165 sequence with a valine substitution at the C-terminus to enhance binding stability (D'Angelo et al., 2018). This complex is primarily expressed on the surface of various tumor cells, including synovial sarcoma and melanoma, while remaining absent from most healthy adult tissues (UniProt P78358). Therapeutic strategies targeting this complex involve engineered T-cell receptor (TCR) therapies and bispecific T-cell engagers that recognize the unique structural interface of the peptide nestled within the HLA-A*02:01 binding groove. By facilitating the direct recognition of intracellular tumor antigens by the immune system, this target enables highly specific T-cell mediated lysis of malignant cells. Drugs like afamitresgene autoleucel have been developed to specifically bind this pMHC to treat advanced solid tumors (FDA, 2024).

Other names

HLA-A*02:01-CTAG1B complexNY-ESO-1:157-165 (V165) peptide-MHC complexSLLMWITQV-HLA-A*02:01HLA-A2/NY-ESO-1

T-cell receptor (TCR) mediated recognition leading to T-cell activation and directed cytotoxicity against cells presenting the specific peptide-MHC complex.