Killer cell lectin-like receptor subfamily K member 1 – UL16-binding protein 1 (NKG2D – ULBP1) (NKG2D – ULBP1)

The KLRK1 (NKG2D) – ULBP1 axis is a critical immune signaling pathway involving the activating receptor NKG2D and its stress-induced ligand ULBP1 [2, 3]. KLRK1 is a C-type lectin-like receptor primarily expressed on natural killer (NK) cells and certain T cell subsets, where it serves to detect and eliminate cells undergoing malignant transformation or viral infection [3, 9]. ULBP1 is an MHC class I-like molecule that is typically absent from healthy tissues but upregulated under conditions of cellular stress, such as DNA damage or oncogenic signaling [2, 11]. The binding of ULBP1 to NKG2D triggers potent cytotoxic responses and cytokine production, facilitating the destruction of target cells [2, 9]. In the context of oncology, this interaction is exploited through the development of CAR-T and CAR-NK therapies, such as CYAD-01, that target NKG2D ligands on tumor surfaces [2]. However, tumors often evade this surveillance by shedding ULBP1 into a soluble form, which can downregulate receptor expression and impair immune function [3, 5, 7].

Other names

KLRK1NKG2DCD314ULBP1RAET1IN2DL-1NKG2D ligand 1UL16-binding protein 1

Activation of NK cell-mediated cytotoxicity and costimulation of T cell responses through the formation of the NKG2D-ULBP1 complex and subsequent signaling via the DAP10 adapter protein [2, 3, 9].