T-cell receptor recognizing gp100 peptide (FLWGPRALV) presented by HLA-A*02:01 (TCR-gp100(476-484))

The T-cell receptor (TCR) recognizing the gp100 peptide FLWGPRALV (residues 476-484) in the context of HLA-A*02:01 is a specialized immune receptor critical for targeting malignant melanoma. gp100, also known as PMEL, is a melanocyte-lineage specific protein involved in melanosome biogenesis that is frequently overexpressed in melanoma cells (Source: UniProt P40967). This specific TCR-peptide-MHC interaction is significant because the FLWGPRALV epitope is a naturally processed, HLA-A2-restricted antigen capable of inducing robust tumor-specific lysis by CD8+ cytotoxic T lymphocytes (Source: PubMed 10438932). Research has specifically highlighted the role of plasmacytoid dendritic cells (pDCs) in presenting this peptide to prime T-cell responses, as pDCs can effectively cross-present melanoma antigens and provide necessary co-stimulation even within the immunosuppressive tumor microenvironment (Source: Cancer Research, Tel et al., 2013). Therapeutic strategies targeting this complex include peptide-based vaccines and TCR-engineered T-cell (TCR-T) therapies designed to expand the repertoire of tumor-reactive T cells in patients. However, clinical application is often challenged by on-target, off-tumor toxicities, such as vitiligo and uveitis, resulting from the presence of gp100 in healthy melanocytes (Source: Journal of Clinical Oncology, 2009).

Other names

gp100-specific T-cell receptorPMEL-specific TCRTCR-gp100:476-484HLA-A*02:01/gp100(476-484) TCRMelanocyte protein PMEL-specific T-cell receptor

The mechanism involves the specific binding of the TCR to the FLWGPRALV peptide presented by HLA-A*02:01, which triggers CD8+ T-cell activation, the secretion of pro-inflammatory cytokines such as IFN-gamma, and the release of cytotoxic granules (perforin and granzymes) to induce apoptosis in gp100-expressing melanoma cells (Source: PubMed 10438932, 15155838).