CD16 antigen, also known as Natural killer cell receptor BY55 and CD16, is a cell membrane protein which contains one Ig-like V-type (immunoglobulin-like) domain. CD16 is a GPI-anchored lymphocyte surface receptor in which expression is mostly restricted to the highly cytotoxic CD56(dim)CD16(+) peripheral blood NK subset. CD16 is a receptor showing broad specificity for both classical and non-classical MHC class I molecules. CD16 is expressed in spleen, peripheral blood, and small intestine. Expression of CD16 is restricted to functional NK and T cytotoxic lymphocytes. CD16 acts as a co-activator receptor for CD3-induced proliferation of CD4+ CD16+ T cells isolated from inflammatory skin lesions. Unique CD4+ CD16+ lymphocyte subset may play a role in the pathogenesis of skin inflammation. Activated NK lymphocytes release a soluble form of CD16 that functionally impairs the MHC-I-specific cytotoxic CD8(+) T lymphocyte responsiveness.