mLama4-specific T-cell receptor (mLama4-specific TCR)

The mLama4-specific T-cell receptor (TCR) is a specialized antigen receptor expressed on CD8+ T cells that specifically recognizes a mutated epitope of the Laminin alpha 4 (Lama4) protein, known as the mLama4 neoantigen (Gubin et al., 2014, Nature). This TCR-antigen pair is a cornerstone of research in the T3 mouse sarcoma model, serving as a paradigm for how the immune system identifies tumor-specific mutations (Theisen et al., 2024, Journal of Immunology). The mLama4 neoantigen is presented by the MHC Class I molecule H2-Kb, and its recognition by the TCR triggers a potent cytotoxic immune response against tumor cells. Studies have shown that T cells bearing high-affinity mLama4-specific TCRs, often utilizing TRBV14 or TRBV13 gene segments, are the primary effectors that expand during successful immune checkpoint blockade therapy. These receptors are currently being investigated as templates for engineered TCR-T cell therapies, which aim to redirect a patient's immune system to target specific neoantigens with high precision. However, a significant therapeutic challenge involves ensuring these TCRs do not cross-react with the wild-type Laminin alpha 4 protein found in normal vascular basement membranes. Overall, the mLama4-specific TCR is a critical tool for studying T-cell repertoire evolution and developing next-generation cancer immunotherapies.

Other names

Laminin alpha 4-specific T-cell receptormLama4-reactive T-cell receptorH2-Kb/mLama4-specific T-cell receptorMutated Laminin alpha 4-specific T-cell receptor

Antigen-specific recognition of the mLama4 neoantigen peptide presented by H2-Kb MHC Class I molecules, triggering T-cell activation, proliferation, and cytotoxic lysis of tumor cells.