Retinoic Acid Early Inducible Genes Define a Ligand Family for the Activating NKG2D Receptor in Mice

Abstract

Here we describe a family of GPI-anchored cell surface proteins that function as ligands for the mouse activating NKG2D receptor. These molecules are encoded by the retinoic acid early inducible (RAE-1) and H60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with MHC class I. Expression of the NKG2D ligands is low or absent on normal, adult tissues; however, they are constitutively expressed on some tumors and upregulated by retinoic acid. Ectopic expression of RAE-1 and H60 confers target susceptibility to NK cell attack. These studies identify a family of ligands for the activating NKG2D receptor on NK and T cells, which may play an important role in innate and adaptive immunity.

Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: Multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal

“…Lectin-like cytotoxicity-activating receptor of activated CD8 + T cells and NK cells [40,41]. CD2 Adhesion molecule involved in T cell immune synapse formation [42,43].…”

Requirements for control of B‐cell lymphoma by NK cells

“…This receptor recognizes self-molecules when these are overexpressed due to infection or malignant transformation [12]. In the mouse, H60, RAE1 and MULT1 were identified as NKG2D ligands (NKG2D-L) [13][14][15]. In summary, the outcome of an NK-cell response is determined by integration of various types of signals arising from sensing distinct self -and nonselfligands.…”

ULBP6/RAET1L is an additional human NKG2D ligand

“…We will follow the ULBP nomenclature from this point. In mouse, NKG2D ligands comprise three members of the H60 family, five members of the Rae1 (retinoic acid early inducible transcript-1) family, and Mult-1 (murine ULBP-like transcript) [14][15][16][17].…”

“…We will follow the ULBP nomenclature from this point. In mouse, NKG2D ligands comprise three members of the H60 family, five members of the Rae1 (retinoic acid early inducible transcript-1) family, and Mult-1 (murine ULBP-like transcript) [14][15][16][17].According to the initial models of NKG2D function, its ligands were thought to be largely absent from healthy cells, but their expression could be induced on viral infection and on tumourigenesis [1]. Ectopic expression of NKG2D ligand leads to anticancer immune responses to transplanted tumours in mice, and the NKG2D knockout mouse has an increased susceptibility to certain types of cancer [18][19][20].…”