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The T-cell receptor (TCR) on Folate Binding Protein (FBP)-specific cytotoxic T lymphocytes is a specialized protein complex responsible for recognizing specific antigenic peptides derived from FBP, also known as Folate Receptor Alpha (FOLR1) (UniProt: P15328; PubMed: 10449132). FBP is a glycosylphosphatidylinositol-anchored glycoprotein that is highly overexpressed in various epithelial malignancies, including ovarian, breast, and lung cancers, while maintaining limited expression in normal tissues (PubMed: 24714518). The TCR on these CTLs typically recognizes FBP-derived epitopes, such as the E39 peptide (FBP 191-199), when presented by Major Histocompatibility Complex (MHC) Class I molecules, specifically HLA-A2 (PubMed: 26933071). Upon binding to the peptide-MHC complex, the TCR initiates a signaling cascade that leads to T-cell activation, proliferation, and the targeted destruction of FBP-expressing tumor cells through the release of cytotoxic granules (PubMed: 29907163). This TCR is a primary focus in the development of adoptive cell therapies, such as TCR-engineered T-cell (TCR-T) therapy, and therapeutic vaccines designed to elicit a robust anti-tumor immune response (ClinicalTrials.gov: NCT04956614). Therapeutic strategies targeting this receptor aim to exploit the high tumor-to-normal tissue expression ratio of FBP to achieve selective tumor clearance while minimizing off-target effects (PubMed: 26044238).
Recognition of FBP-derived peptides presented by MHC Class I (HLA-A2) on tumor cells, leading to CTL activation and targeted cell lysis.
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