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The Journal of Immunology, Vol 151, Issue 1 60-70, Copyright © 1993 by American Association of Immunologists
ARTICLES |
BA Garni-Wagner, A Purohit, PA Mathew, M Bennett and V Kumar
Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas 75235.
NK cells and IL-2-propagated splenic T cells mediate non-MHC-restricted cytotoxicity. The molecules involved in this process are not well defined. We describe a novel 66-kDa cell surface molecule called 2B4 that is expressed on cells that mediate non-MHC-restricted cytotoxicity. All resting and rIL-2 cultured NK cells and a significant number of T cells cultured in high doses of rIL-2 are 2B4+. In fresh as well as cultured spleen cells, all non-MHC-restricted cytotoxicity is contained within the 2B4+ population. In addition to defining cells capable of non-MHC-restricted killing, the 2B4 molecule is also involved in modulation of their function. In the presence of anti-2B4, the lytic activity of cultured NK cells and non-MHC-restricted T cells against a wide variety of FcR- and FcR+ targets is greatly augmented. Anti-2B4 is also able to transduce other signals in IL-2-activated NK cells such as IFN-gamma secretion and granule exocytosis. In addition, 2B4+ T cells can specifically lyse the 2B4 hybridoma cells. Unlike many other activation and adhesion molecules (such as murine CD2, LFA-1, and CD16), 2B4 expression is restricted to cells that mediate NK-like killing. Conversely, highly activated T cells that do not express 2B4 do not mediate non-MHC-restricted killing. Together these data suggest that the 2B4 molecule is likely to be a part of a receptor complex or a component of signal-transducing complex on cells that mediate non-MHC- restricted killing.
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S. S. Chuang, H.-T. K. Pham, P. R. Kumaresan, and P. A. Mathew A Prominent Role for Activator Protein-1 in the Transcription of the Human 2B4 (CD244) Gene in NK Cells J. Immunol., May 15, 2001; 166(10): 6188 - 6195. [Abstract] [Full Text] [PDF]
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C. Watzl, C. C. Stebbins, and E. O. Long Cutting Edge: NK Cell Inhibitory Receptors Prevent Tyrosine Phosphorylation of the Activation Receptor 2B4 (CD244) J. Immunol., October 1, 2000; 165(7): 3545 - 3548. [Abstract] [Full Text] [PDF]
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L. Benoit, X. Wang, H. F. Pabst, J. Dutz, and R. Tan Cutting Edge: Defective NK Cell Activation in X-Linked Lymphoproliferative Disease J. Immunol., October 1, 2000; 165(7): 3549 - 3553. [Abstract] [Full Text] [PDF]
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S. G. Tangye, J. H. Phillips, L. L. Lanier, and K. E. Nichols Cutting Edge: Functional Requirement for SAP in 2B4-Mediated Activation of Human Natural Killer Cells as Revealed by the X-Linked Lymphoproliferative Syndrome J. Immunol., September 15, 2000; 165(6): 2932 - 2936. [Abstract] [Full Text] [PDF]
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L. L. Lanier Turning On Natural Killer Cells J. Exp. Med., April 10, 2000; 191(8): 1259 - 1262. [Full Text] [PDF]
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F. Colucci, M. Turner, E. Schweighoffer, D. Guy-Grand, V. Di Bartolo, M. Salcedo, V. L. J. Tybulewicz, and J. P. Di Santo Redundant Role of the Syk Protein Tyrosine Kinase in Mouse NK Cell Differentiation J. Immunol., August 15, 1999; 163(4): 1769 - 1774. [Abstract] [Full Text] [PDF]
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M. K. Wild, A. Cambiaggi, M. H. Brown, E. A. Davies, H. Ohno, T. Saito, and P. A. van der Merwe Dependence of T Cell Antigen Recognition on the Dimensions of an Accessory Receptor–Ligand Complex J. Exp. Med., July 5, 1999; 190(1): 31 - 42. [Abstract] [Full Text] [PDF]
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S. G. Tangye, S. Lazetic, E. Woollatt, G. R. Sutherland, L. L. Lanier, and J. H. Phillips Cutting Edge: Human 2B4, an Activating NK Cell Receptor, Recruits the Protein Tyrosine Phosphatase SHP-2 and the Adaptor Signaling Protein SAP J. Immunol., June 15, 1999; 162(12): 6981 - 6985. [Abstract] [Full Text] [PDF]
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J. D. Schatzle, S. Sheu, S. E. Stepp, P. A. Mathew, M. Bennett, and V. Kumar Characterization of inhibitory and stimulatory forms of the murine natural killer cell receptor 2B4 PNAS, March 30, 1999; 96(7): 3870 - 3875. [Abstract] [Full Text] [PDF]
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J. Gonzalez-Cabrero, C. J. Wise, Y. Latchman, G. J. Freeman, A. H. Sharpe, and H. Reiser CD48-deficient mice have a pronounced defect in CD4+ T cell activation PNAS, February 2, 1999; 96(3): 1019 - 1023. [Abstract] [Full Text] [PDF]
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A. H. Idris, K. Iizuka, H. R.C. Smith, A. A. Scalzo, and W. M. Yokoyama Genetic Control Of Natural Killing and In Vivo Tumor Elimination by the Chok Locus J. Exp. Med., December 21, 1998; 188(12): 2243 - 2256. [Abstract] [Full Text] [PDF]
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M. H. Brown, K. Boles, P. Anton van der Merwe, V. Kumar, P. A. Mathew, and A. Neil Barclay 2B4, the Natural Killer and T Cell Immunoglobulin Superfamily Surface Protein, Is a Ligand for CD48 J. Exp. Med., December 7, 1998; 188(11): 2083 - 2090. [Abstract] [Full Text] [PDF]
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Y. Latchman, P. F. McKay, and H. Reiser Cutting Edge: Identification of the 2B4 Molecule as a Counter-Receptor for CD48 J. Immunol., December 1, 1998; 161(11): 5809 - 5812. [Abstract] [Full Text] [PDF]
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N. S. Williams, T. A. Moore, J. D. Schatzle, I. J. Puzanov, P.V. Sivakumar, A. Zlotnik, M. Bennett, and V. Kumar Generation of Lytic Natural Killer 1.1+, Ly-49- Cells from Multipotential Murine Bone Marrow Progenitors in a Stroma-free Culture: Definition of Cytokine Requirements and Developmental Intermediates J. Exp. Med., November 3, 1997; 186(9): 1609 - 1614. [Abstract] [Full Text] [PDF]
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