The Journal of Experimental Medicine
Track the topics, authors and articles important to you
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 3 May 2004. doi:10.1084/jem.20031989
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 9, 1245-1254
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 181K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, K.-M.
Right arrow Articles by Kumar, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, K.-M.
Right arrow Articles by Kumar, V.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
2B4 Acts As a Non–Major Histocompatibility Complex Binding Inhibitory Receptor on Mouse Natural Killer Cells

Kyung-Mi Lee1, Megan E. McNerney2, Susan E. Stepp4, Porunelloor A. Mathew5, John D. Schatzle6, Michael Bennett6, and Vinay Kumar3

1 Department of Biochemistry, Korea University College of Medicine, Seoul 136-705, Korea
2 Committee on Immunology and 3 Department of Pathology, University of Chicago, Chicago, IL 60637
4 Pathology, University of Massachusetts Medical School, Worcester, MA 01655
5 Molecular Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107
6 Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390

Address correspondence to Kyung-Mi Lee, Department of Biochemistry, Korea University College of Medicine, Sungbuk-Gu, Anam-Dong, Seoul 136-705, Korea. Phone: 011-822-920-6409; Fax: 011-822-928-4853; email: kyunglee{at}korea.ac.kr

Natural killer (NK) cells are critical in the immune response to tumor cells, virally infected cells, and bone marrow allografts. 2B4 (CD244) is expressed on all NK cells and the ligand for 2B4, CD48, is expressed on hematopoietic cells. Cross-linking 2B4 on NK cells with anti-2B4 monoclonal antibody leads to NK cell activation in vitro. Therefore, 2B4 is considered to be an activating receptor. Surprisingly, we have found, using antibody-blocking and 2B4-deficient NK cells, that NK lysis of CD48+ tumor and allogeneic targets is inhibited by 2B4 ligation. Interferon {gamma} production by NK cells is also inhibited. Using a peritoneal tumor clearance assay, it was found that 2B4–/– mice have increased clearance of CD48+ tumor cells in vivo. Retroviral transduction of 2B4 was sufficient to restore inhibition in 2B4–/– primary NK cells. It was found that although mature NK cells express SH2D1A, in vitro–derived NK cells do not. However, both populations are inhibited by 2B4 ligation. This indicates that 2B4 inhibitory signaling occurs regardless of the presence of SH2D1A. These findings reveal a novel role for 2B4 as a non–major histocompatibility complex binding negative regulator of NK cells.

Key Words: CD48 • CD150 • tumor • IFN-{gamma} • innate immunity

K.-M. Lee and M.E. McNerney contributed equally to this work.

Abbreviations used in this paper: ADCC, antibody-dependent cellular cytotoxicity; CFSE, carboxyl fluorescein succinimidyl ester; EAT-2, EWS-activated transcript 2; ITIM, immunoreceptor tyrosine-based inhibition motif; ITSM, immunoreceptor tyrosine-based switch motif; LAK, lymphokine-activated killer; XLP, X-linked lymphoproliferative disorder.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS