The CD2 family of natural killer cell receptors.

The CD2 family of receptors is evolutionarily conserved and widely expressed on cells within the hematopoietic compartment. In recent years several new members have been identified with important roles in the immune system. CD2 family members regulate natural killer (NK) cell lytic activity and inflammatory cytokine production when engaged by ligands on tumor cells. Furthermore, a subfamily of CD2 receptors, the CD 150-like molecules, has been implicated in the pathogenesis of X-linked lymphoproliferative disease (XLP). Many of these receptors have now been shown to bind homophilically or heterophilically to other molecules within the family. With these discoveries a novel mechanism for lymphocyte regulation has emerged: CD2 family members on NK cells engage ligands on neighboring NK cells, leading to NK cell stimulation. Moreover, heterotypic stimulatory interactions between NK cells and other leukocytes also occur. In this manner, CD2 family members may provide interlymphocyte communication that maintains organization within the hematopoietic compartment and amplifies immune responses. This review discusses these multiple roles for CD2 family members, focusing specifically on the regulation of NK cells.