|
|
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.
 Previous Article | Next Article 
Submitted January 14, 2005
Accepted April 27, 2005
Requirement of homotypic NK cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions
Kyung-Mi Lee*, John P Forman, Megan E McNerney, Susan Stepp, Sumalatha Kuppireddi, Dustin Guzior, Yvette E Latchman, Mohamed H Sayegh, Hideo Yagita, Chul-Kyu Park, Seog Bae Oh, Christoph Wulfing, John Schatzle, Porunelloor A Mathew, Arlene H Sharpe, and Vinay Kumar
Department of Pathology, University of Chicago, Chicago, IL, USA; Department of Biochemistry and Division of Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Seoul, Korea, Republic of
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Department of Pathology, University of Chicago, Chicago, IL, USA
Center for Immunology, Department of Cell Biology and Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
Department of Physiology, College of Dentistry, Seoul National University, Seoul, Korea, Republic of
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA
* Corresponding author; email: kyunglee{at}korea.ac.kr.
2B4 belongs to the CD2 subset of the IgG family of receptors. Members in this family have been shown to function as co-receptors via homophilic or heterophilic interactions. Both 2B4 and CD2 bind to CD48, another member of this family. Since all three molecules are expressed on 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-g seceretion upon 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 2B4/CD48 interactions.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. G. Clarkson and M. H. Brown
Inhibition and Activation by CD244 Depends on CD2 and Phospholipase C-{gamma}1
J. Biol. Chem.,
September 11, 2009;
284(37):
24725 - 24734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Altvater, S. Landmeier, S. Pscherer, J. Temme, K. Schweer, S. Kailayangiri, D. Campana, H. Juergens, M. Pule, and C. Rossig
2B4 (CD244) Signaling by Recombinant Antigen-specific Chimeric Receptors Costimulates Natural Killer Cell Activation to Leukemia and Neuroblastoma Cells
Clin. Cancer Res.,
August 1, 2009;
15(15):
4857 - 4866.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Taniguchi, D. Guzior, and V. Kumar
2B4 inhibits NK-cell fratricide
Blood,
September 15, 2007;
110(6):
2020 - 2023.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. G. Clarkson, S. J. Simmonds, M. J. Puklavec, and M. H. Brown
Direct and Indirect Interactions of the Cytoplasmic Region of CD244 (2B4) in Mice and Humans with FYN Kinase
J. Biol. Chem.,
August 31, 2007;
282(35):
25385 - 25394.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Munitz, I. Bachelet, F. D. Finkelman, M. E. Rothenberg, and F. Levi-Schaffer
CD48 Is Critically Involved in Allergic Eosinophilic Airway Inflammation
Am. J. Respir. Crit. Care Med.,
May 1, 2007;
175(9):
911 - 918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
