title: 2B4 (CD244) is a non-MHC binding receptor with multiple functions on natural killer cells and CD8+ T cells.
abstract: 2B4 (CD244) is expressed by memory-phenotype CD8(+) T cells and all natural killer (NK) cells. The ligand for 2B4, CD48, is expressed on hematopoietic cells. 2B4 is conserved in humans and mice, and a number of reports have linked 2B4 with activation of lymphocytes. We have employed 2B4-deficient mice and antibody blocking to analyze 2B4 function both in vitro and in vivo and found that 2B4 is a receptor with multiple functions. 2B4 is required for optimal activation of CD8(+) T cells and NK cells--in this context 2B4 requires interaction with CD48 on neighboring lymphocytes, demonstrating that homotypic interaction within NK cell or T cell populations augments immunity. When 2B4 is engaged by CD48 on a target cell, 2B4 conversely inhibits NK effector function. As an inhibitory receptor, 2B4 is unconventional as it is not regulated by MHC class I molecules. In this review we will discuss the significance of these multiple functions and the events that may regulate differential 2B4 signaling outcome.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA. mcnerney@midway.uchicago.edu
authors.forename: Megan E
authors.initials: ME
authors.lastname: McNerney
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Vinay
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019143:Evolution, Molecular; D006023:Glycoproteins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; C490007:Cd244a protein, mouse; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1