Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. KLRD1 (CD94) is an antigen preferentially expressed on NK cells and is classified as a type II membrane protein because it has an external C terminus. KLRC1 (NKG2A) is also a type II transmembrane protein which dimerizes with CD94. CD94 contains a short cytoplasmic domain that is responsible for signal transduction. CD94/NKG2 is part of a family of C-type lectin receptors which are expressed predominantly on the surface of NK cells and a subset of CD8+ T-lymphocyte. These receptors stimulate or inhibit cytotoxic activity of NK cells, therefore they are divided into activating and inhibitory receptors according to their function. CD94/NKG2 recognize non-classical MHC glycoproteins class I (HLA-E in human and Qa-1 molecules in the mouse). The NKG2A receptor transmits inhibitory signals through two immuno-receptor tyrosine-based inhibitory motifs (ITIM) in the cytoplasmic tail that are defined by the sequence (I/L/V/S)xYxx(L/V), where “x” means any amino acid at a given position. When ITIM-bearing receptors engage their ligand, Src family kinases phosphorylate tyrosine residues, which in turn allows recruitment of the tyrosine phosphatase SHP-1, SHP-2 or SHIP. It leads to de-phosphorylation of tyrosine kinase’s substrates, which are involved in activating cascades. As a result, NK cell activation is suppressed.
Protein expression analysis in NK cells
Strain specific CD94 and NKG2A expression analysis in homozygous B-hCD94/hNKG2A mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hCD94/hNKG2A (H/H) mice, and analyzed by flow cytometry with species-specific CD94 or NKG2A antibody. Mouse CD94 and NKG2A were detectable in WT mice. Human CD94 and NKG2A were exclusively detectable in homozygous B-hCD94/hNKG2A but not WT mice. (Monalizumab was used to detect the human NKG2A protein in WT and homozygous B-hCD94/hNKG2A)