Activating interactions in human NK cell recognition: the role of 2B4-CD48.
2B4 is a cell surface glycoprotein of the immunoglobulin superfamily structurally related to CD2-like molecules. It was originally identified in the mouse as a receptor that mediates non-MHC-restricted cytotoxicity by NK cells and CD8+ T cells. Recently, 2B4 was shown to bind CD48 by molecular binding assays and surface plasmon resonance. Here, we have investigated the cell surface expression, biochemical characteristics and function of human 2B4. Our results show that 2B4 is expressed not only on NK cells and CD8+ T cells, but also on monocytes and basophils, indicating a broader role for 2B4 in leukocyte activation. In NK cells, engagement of 2B4 with a specific monoclonal antibody or with CD48 can trigger NK cell-mediated cytotoxicity. The contribution of 2B4-CD48 interaction to target cell lysis by different NK cell clones varies, probably dependent on the relative contribution of other receptor-ligand interactions. In T cells and monocytes, ligation of 2B4 does not lead to T cell or monocyte activation. Thus, it appears that the primary function of 2B4 is to modulate other receptor-ligand interactions to enhance leukocyte activation.
Nakajima
H
H
Basel Institute for Immunology, Switzerland. nakajima@bii.ch
Cella
M
M
Langen
H
H
Friedlein
A
A
Colonna
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000071178:CD48 Antigen; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D019169:Jurkat Cells; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C084093:CD244 protein, human; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D007136:Immunoglobulins; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family