T-cell receptor recognizing HLA-A*0201-melanoma antigen peptide complexes (TCR-HLA-A2-Melanoma)

The T-cell receptor (TCR) recognizing HLA-A*0201–Melan-A/gp100/tyrosinase peptide complexes is a specialized immune receptor that identifies melanoma-associated differentiation antigens (MDAs) presented by the Class I Major Histocompatibility Complex (MHC) allele HLA-A*02:01 (PMID: 8171339, PMID: 8171338). These TCRs are central to the development of adoptive cell therapies, including tumor-infiltrating lymphocyte (TIL) therapy and engineered TCR-T cell therapies, which aim to harness the immune system to eliminate melanoma cells (PMID: 21892161). Melan-A (MART-1), gp100, and tyrosinase are proteins involved in melanin biosynthesis and are highly expressed in both normal melanocytes and malignant melanoma, making them attractive targets for immunotherapy (PMID: 8358930). When the TCR binds to its specific peptide-HLA complex, it initiates a signaling cascade through the CD3 complex, resulting in T-cell proliferation, secretion of pro-inflammatory cytokines like IFN-gamma, and the induction of apoptosis in the target tumor cell (PMID: 29330111). Therapeutic agents such as tebentafusp, a bispecific gp100-peptide-HLA-directed T-cell engager, utilize this recognition mechanism to treat metastatic uveal melanoma (PMID: 34551229). However, because these antigens are also expressed in healthy melanocytes, safety concerns include on-target off-tumor toxicities affecting the skin, eyes, and inner ear (PMID: 19139330).

Other names

MART-1-specific T-cell receptorgp100-specific T-cell receptorTyrosinase-specific T-cell receptorMelanoma-associated antigen-specific TCRHLA-A*02:01-restricted TCR

T-cell receptor-mediated recognition of specific peptide-MHC complexes on the surface of tumor cells, leading to T-cell activation and cytotoxic destruction of the target cell.