Baculoviral IAP repeat-containing protein 5-derived peptide–HLA class I complex (Survivin-HLA-I complex)

Baculoviral IAP repeat-containing protein 5-derived peptide–HLA class I complexes (Survivin-HLA-I) are cell-surface molecular assemblies consisting of a short peptide fragment derived from the survivin protein bound to a Human Leukocyte Antigen (HLA) class I molecule (Schmitz et al., 2000). Survivin is a member of the inhibitor of apoptosis (IAP) family that is highly expressed in most human cancers but nearly undetectable in normal differentiated adult tissues, making its processed peptides ideal targets for immunotherapy (Altieri, 2003). These complexes are presented on the surface of malignant cells and are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs). Therapeutic strategies targeting these complexes include peptide vaccines, such as SurVaxM, and engineered TCR-T cell therapies designed to trigger a specific immune response against tumor cells (Ahluwalia et al., 2023; Fenstermaker et al., 2016). Because survivin plays a critical role in both inhibiting apoptosis and regulating the cell cycle, targeting its presentation on HLA molecules allows the immune system to selectively eliminate cells with high proliferative and anti-apoptotic potential. However, challenges include the heterogeneity of HLA expression and the potential for immune evasion through the downregulation of the antigen presentation machinery (Wheatley & Altieri, 2019).

Other names

Survivin-derived peptide–HLA class I complexBIRC5 peptide-MHC complexSurvivin-pMHCSurvivin-HLA-A*02:01 complexSurvivin-MHC class I complexSurvivin-HLA complex

Activation and expansion of antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) that recognize the specific survivin peptide fragment presented within the HLA class I groove on the tumor cell surface, leading to targeted cell lysis and apoptosis (Ahluwalia et al., 2023; Schmitz et al., 2000).