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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3181-3188. Prepublished online as a Blood First Edition Paper on May 19, 2005; DOI 10.1182/blood-2005-01-0185.
IMMUNOBIOLOGY Requirement of homotypic NK-cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functionsFrom the Department of Pathology, University of Chicago, Chicago, IL; the Department of Biochemistry and Division of Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Seoul, Korea; the Department of Medicine, Brigham and Women's Hospital, Boston, MA; the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX; the Center for Immunology, Departments of Cell Biology and Pathology, University of Texas Southwestern Medical Center, Dallas, TX; the Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; and the Department of Physiology, College of Dentistry, Seoul National University, Seoul, Korea.
2B4 belongs to the CD2 subset of the IgG family of receptors. Members in this family have been shown to function as coreceptors via homophilic or heterophilic interactions. Both 2B4 and CD2 bind to CD48, another member of this family. Because all 3 molecules are expressed on natural killer (NK) cells, it raises a possibility that the binding of 2B4 and CD2 to CD48 among NK cells may have functional consequences. Using specific monoclonal antibodies and gene-deficient NK cells, we found that 2B4/CD48, but not CD2/CD48, interaction is essential for IL-2–driven expansion and activation of murine NK cells. In the absence of 2B4/CD48 interaction, NK cytotoxicity and IFN-
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| Copyright © 2006 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
secretion on tumor target exposure is severely impaired. Impaired activation of NK cells in 2B4-deficient mice was also demonstrated by poor NK-mediated clearance of syngeneic tumor cells in these mice. Functional impairment of NK cells in the absence of 2B4/CD48 interactions was accompanied by defective calcium signaling, suggesting that the early signaling pathway of NK receptors is inhibited. Finally, homotypic interactions among NK cells through 2B4/CD48 was visualized by specific localization of GFP-tagged 2B4 onto NK-NK conjugation sites. Thus, these data identify a novel mechanism whereby NK effector function is regulated via homotypic 2B4/CD48 interactions. 
