Tumor necrosis factor ligand superfamily member 8 peptide-MHC complex (TNFSF8-MHC)

Tumor Necrosis Factor Ligand Superfamily Member 8 (TNFSF8), also known as CD153, is a type II transmembrane protein that serves as the ligand for CD30 (TNFRSF8) (UniProt: P32971). It is primarily expressed on activated T cells, B cells, and monocytes, where it plays a role in cell proliferation and apoptosis (NCBI Gene ID: 944). In various hematologic malignancies, such as Hodgkin lymphoma and anaplastic large cell lymphoma, TNFSF8 is significantly overexpressed, contributing to tumor pathogenesis. The presentation of TNFSF8-derived peptide epitopes by Major Histocompatibility Complex (MHC) molecules allows these intracellularly processed fragments to be recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes. This makes the TNFSF8-MHC complex a specific target for advanced immunotherapies, including TCR-engineered T cells (TCR-T) and TCR-like antibodies, which can direct an immune response specifically against malignant cells. Such strategies are designed to overcome the limitations of traditional antibody therapies by targeting the cell's internal proteome as displayed on the surface via MHC. Potential safety concerns include off-target reactivity if the peptide sequence is shared with proteins in healthy tissues, as well as cytokine release syndrome associated with potent T-cell activation.

Other names

CD153-MHC complexTNFSF8-HLA complexCD153 peptide-MHCTumor necrosis factor ligand superfamily member 8 peptide-derived epitopes presented by MHC

Recognition of specific peptide-MHC complexes by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce targeted cell lysis.