UL16-Binding Protein Family Ligand (ULBP1–6) (ULBP1-6)

The UL16-binding protein (ULBP) family, comprising ULBP1 through ULBP6, represents a group of cell surface glycoproteins that are structurally related to MHC class I molecules and serve as ligands for the activating immune receptor NKG2D, which is expressed on natural killer (NK) cells and certain T-cell subsets. ULBPs are stress-induced ligands, upregulated in response to cellular stress such as infection or transformation, triggering activation signals in NK cells or cytotoxic T lymphocytes, leading to immune effector functions including cytotoxicity against target cells. High expression of certain ULBPs has been observed in various hematologic malignancies and solid tumors making them attractive targets for immunotherapeutic strategies such as CAR-T therapies targeting NKG2D ligands. HCMV can evade this mechanism through the protein UL16.

Other names

ULBP1ULBP2ULBP3ULBP4ULBP5ULBP6RAET1I (ULBP1)RAET1H (ULBP2)RAET1N (ULBP3)NKG2DL1 (ULBP1)

ULBPs engage NKG2D receptors → activate DAP10 adaptor → trigger downstream signaling cascades: JAK/STAT, ERK/MAPK, PI3K/Akt. This leads to enhanced NK cell-mediated lysis, increased cytokine secretion (especially IFN-gamma when synergizing with IL‑12), and overcoming inhibitory signals from self-MHC recognition by NK cells.