HLA-A*02:01-survivin (95-104) peptide-MHC complex (HLA-A*02:01/Survivin(95-104))

The HLA-A*02:01-survivin (95-104) complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy. It consists of the HLA-A*02:01 molecule presenting a decamer peptide (ELTLGEFLKL) derived from the survivin protein (Schmitz et al., 2000, PMID: 11156515). Survivin, also known as baculoviral IAP repeat-containing protein 5 (BIRC5), is a member of the inhibitor of apoptosis (IAP) family that is overexpressed in nearly all human cancers but has minimal expression in normal adult tissues (Altieri, 2003, PMID: 12738720). This differential expression makes the complex an ideal target for cytotoxic T lymphocytes (CTLs) which can recognize the pMHC on the surface of malignant cells. Therapeutic approaches targeting this complex include peptide-based vaccines, such as the Survivin-95-104 vaccine, and the development of T-cell receptor (TCR) engineered T-cell therapies (Wobser et al., 2006, PMID: 16707590). Clinical application requires patient screening for the HLA-A*02:01 allele and confirmation of survivin expression within the tumor. Potential challenges include the risk of off-target toxicity if the TCR cross-reacts with similar self-peptides and the development of resistance through antigen loss or HLA downregulation. This target is particularly relevant in melanoma, glioblastoma, and various solid tumors where survivin plays a key role in cell survival and treatment resistance.

Other names

HLA-A*02:01-ELTLGEFLKLSurvivin-95-104/HLA-A*02:01 complexBIRC5(95-104)-HLA-A*02:01Survivin-A2 complexBaculoviral IAP repeat-containing protein 5 (95-104) presented by HLA-A*02:01

The complex acts as a ligand for the T-cell receptor (TCR) on CD8+ cytotoxic T lymphocytes. Therapeutic intervention involves using vaccines to expand endogenous T-cells or engineering T-cells with specific TCRs to recognize this pMHC, triggering directed cell lysis of survivin-expressing tumor cells via the release of perforins and granzymes.