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The MHC-presented LY6K-177 peptide recognized by T-cell receptors is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. The peptide, typically the 10-mer RYCNLEGPPI (residues 177–186), is derived from the Lymphocyte antigen 6 complex, locus K (LY6K) protein, which is a well-characterized cancer-testis antigen (CTA) [1, 3]. In many cancers, including lung, esophageal, and gastric carcinomas, LY6K is significantly overexpressed, whereas its expression in normal tissues is largely restricted to the immune-privileged testis [2, 6]. This peptide is presented on the cell surface by the HLA-A*24:02 molecule, where it is recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes (CTLs) [7, 10]. Therapeutic targeting of this complex primarily involves peptide-based vaccines, often administered with adjuvants like Montanide ISA 51 or CpG-7909, to elicit a robust, tumor-specific CTL response [9, 12]. Clinical trials have demonstrated that vaccination can induce peptide-specific immune responses and improve survival outcomes in patients with HLA-A*24:02-positive advanced cancers [3, 11]. Because of its high tumor specificity and restricted normal tissue expression, the LY6K-177/MHC complex is considered a promising target for both vaccines and adoptive T-cell therapies, such as TCR-engineered T cells [1, 13].
Induction of antigen-specific cytotoxic T lymphocytes (CTLs) that recognize the LY6K-177 peptide presented by HLA-A*24:02 on tumor cells, leading to targeted cell lysis.
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