2B4-mediated activation of human natural killer cells

2B4 is a member of the CD2 subset of the immunoglobulin superfamily of cell surface receptors. Other members of this family include CD2, CD48, CD58, C D84, signaling lymphocytic activation molecule and Ly-9. Some of these mole cules are activating structures expressed by natural killer cells and T cel ls. We have recently cloned and characterised the human homologue of 2B4 an d found that the cytoplasmic domain of 2B4 can interact with SAP, a signali ng adaptor protein that is mutated in the immunodeficiency X-linked lymphop roliferative disease (XLP). Additionally, the natural ligand of 2B4 has bee n identified as CD48. These findings have facilitated the investigation of the functional role of this receptor-ligand pair, and associated signal tra nsduction pathways, on immune cells. In this study, it was found that the i nteraction between 2B4 on effector cells and CD48 on target cells induced N K-cell activation, as evidenced by increased cytotoxicity and secretion of IFN-gamma. The responses induced by ligation of 2B4 could be reduced by the co-ligation of inhibitory receptors expressed by NK cells, demonstrating t hat activation signals delivered via 2B4 can be regulated by the action of certain inhibitory receptors. Because the signalling pathway of 2B4 involve s SAP, it is possible that 2B4-mediated NK-cell activation may be compromis ed in patients with XLP due to mutations in SAP. This may contribute to the phenotype and progression of this disease. (C) 2000 Elsevier Science Ltd. All rights reserved.