UL16-binding protein family (ULBP) (ULBP)

The UL16-binding protein (ULBP) family, also known as the Retinoic Acid Early Transcript 1 (RAET1) family, consists of several MHC class I-related cell surface glycoproteins (ULBP1-6) that function as ligands for the NKG2D activating receptor (Cosman et al., 2001, Immunity). These proteins are generally not expressed on healthy tissues but are highly upregulated under conditions of cellular stress, such as DNA damage, viral infection, or oncogenic transformation (Schmiedel & Mandelboim, 2018, Frontiers in Immunology). This induced-self expression pattern makes them critical markers for immune surveillance, allowing Natural Killer (NK) cells and CD8+ T cells to identify and destroy compromised cells (Spear et al., 2013, Cancer Immunity). In oncology, ULBPs are frequently overexpressed, making them promising targets for various immunotherapeutic approaches, including Chimeric Antigen Receptor (CAR) T-cell therapies like CYAD-01 and bispecific antibodies (Celyad Oncology, 2023). However, many tumors evade this immune recognition by proteolytically shedding ULBPs from the cell surface, creating soluble decoys that block NKG2D receptors and impair effector cell function (Fernández-Messina et al., 2010, Blood). Therapeutic strategies often focus on either targeting the membrane-bound forms or inhibiting the shedding process to restore immune sensitivity.

Other names

RAET1 proteinsRetinoic acid early transcript 1 familyNKG2D ligandsULBP1-6UL16-binding proteins

Activation of the NKG2D receptor on effector immune cells (NK cells and T cells) to induce targeted lysis of cells expressing ULBP ligands.