Survivin-derived HLA-A*02 peptide–T cell receptor complex (Survivin-HLA-A2-TCR)

The Survivin-derived HLA-A2 peptide–T cell receptor complex is a tripartite molecular assembly central to the cellular immune response against cancer (Altieri, 2008). Survivin, encoded by the BIRC5 gene, is a member of the inhibitor of apoptosis (IAP) family that is highly expressed in most human malignancies but nearly absent in differentiated normal tissues (Andersen et al., 2001). In this complex, a specific peptide fragment of Survivin, such as the Sur9 or Sur1M epitopes, is presented on the cell surface by the Human Leukocyte Antigen A*02 (HLA-A2) molecule. This peptide-MHC (pMHC) complex is then specifically recognized by the T cell receptor (TCR) of CD8+ cytotoxic T lymphocytes (Shirasu et al., 2013). Recognition of this complex triggers T cell activation, leading to the release of cytotoxic granules that induce apoptosis in the target tumor cell. Therapeutic strategies targeting this complex include TCR-engineered T cell (TCR-T) therapies and peptide vaccines like SurVaxM, which aim to redirect the immune system to selectively eliminate Survivin-expressing tumor cells (Fenstermaker et al., 2016). Because Survivin is essential for tumor cell survival and division, targeting this complex provides a mechanism to attack a broad range of cancers while potentially minimizing escape through antigen loss. Clinical development of drugs targeting this complex focuses on various solid tumors and hematologic malignancies where Survivin and HLA-A2 are co-expressed.

Other names

BIRC5-HLA-A*02:01-TCR complexSurvivin-MHC-TCR complexSurvivin-peptide-MHC-TCR complexSur9-HLA-A2-TCR complex

TCR-mediated recognition of the Survivin peptide-HLA-A2 complex leads to the activation of cytotoxic T lymphocytes and the targeted destruction of Survivin-expressing tumor cells (Andersen et al., 2001; Shirasu et al., 2013).