T-cell receptor recognizing Carcinoembryonic antigen peptide 1 (CAP-1) in complex with HLA-A*02:01 (TCR-CAP-1/HLA-A2)

The T-cell receptor (TCR) recognizing the CAP-1/HLA-A2 complex is a specialized immune receptor found on cytotoxic T lymphocytes (CTLs) that specifically identifies a 9-amino acid peptide derived from Carcinoembryonic Antigen (CEA). CEA is a well-characterized tumor-associated antigen that is highly overexpressed in various adenocarcinomas, particularly colorectal, pancreatic, and lung cancers. The CAP-1 peptide (YLSGANLNL) is presented on the cell surface by the Human Leukocyte Antigen A*02:01 (HLA-A2) molecule, serving as a signature for malignant cells. When the TCR binds to this specific peptide-MHC complex, it triggers a signaling cascade that activates the CTL to release cytotoxic granules, such as perforin and granzymes, resulting in the destruction of the tumor cell. In therapeutic contexts, this TCR is a primary focus for TCR-engineered T-cell (TCR-T) therapies and cancer vaccines designed to enhance the immune system's ability to eliminate CEA-positive tumors. However, because CEA is also expressed at lower levels in normal mucosal tissues, a significant challenge in targeting this receptor is managing on-target off-tumor toxicities, such as severe inflammatory responses in the gut.

Other names

CEA-specific T-cell receptorCAP-1-specific TCRT-cell receptor recognizing CEA peptide 605-613Carcinoembryonic antigen-specific TCRTCR recognizing YLSGANLNL/HLA-A*02:01

Antigen-specific recognition of the CAP-1 peptide (YLSGANLNL) presented by HLA-A*02:01 on tumor cells, leading to T-cell activation, cytokine release, and granzyme/perforin-mediated lysis of the target cell.