CD160 is a cell surface glycoprotein of immunoglobulin superfamily, which functions as a costimulatory receptor expressed mainly on cytotoxic cell populations and recognizing both classical and non-classical MHC class I molecules. It can form disulfide-linked multimers. Down-modulation of CD160 occurs as a consequence of its proteolytic cleavage and the released soluble form was found to impair the MHC-class I specific cytotoxicity of CD8+ T lymphocytes and NK cells. In contrast to GPI-anchored isoform with broader expression among CD160 positive cells, expression of the transmembrane isoform is restricted to NK cells and is activation-dependent.