Killer cell lectin-like receptor subfamily B member 1 (CD161) (KLRB1)

Killer cell lectin-like receptor subfamily B member 1, commonly known as CD161, is a type II transmembrane glycoprotein and a member of the C-type lectin-like receptor family. It is predominantly expressed on natural killer (NK) cells and specific subsets of T cells, including Th17 cells, MAIT cells, and a subset of cytotoxic CD8+ T cells. CD161 acts as a key regulator of immune function; while it can provide co-stimulatory signals in certain contexts, recent evidence highlights its role as an inhibitory checkpoint in the tumor microenvironment, where its interaction with the ligand CLEC2D (LLT1) suppresses T-cell effector functions. In the context of autoimmunity, CD161 is a marker for 'pathogenic' T cells that produce high levels of pro-inflammatory cytokines like IL-17 and IFN-gamma, contributing to tissue damage in diseases such as multiple sclerosis and Crohn's disease. Therapeutic strategies currently focus on blocking the CD161-CLEC2D pathway to reinvigorate anti-tumor immunity or targeting CD161+ cells to dampen chronic inflammation.

Other names

CD161CLEC5BNKR-P1ANatural killer cell surface protein P1AHNKR-P1A

Blockade of the inhibitory interaction between CD161 and its ligand CLEC2D (LLT1) to enhance T-cell and NK-cell mediated anti-tumor cytotoxicity; or depletion of pathogenic CD161-expressing Th17 cells in autoimmune contexts.