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PMID: 15870174 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

2B4 (CD244)-CD48 interactions provide a novel MHC class I-independent system for NK-cell self-tolerance in mice.

Blood ·Vol. 106 ·No. 4 ·2005-08-15 ·Pages 1337-40

McNerney ME, Guzior D, Kumar V

Abstract

Natural killer (NK) cells must be able to eliminate infected and transformed cells while remaining tolerant of normal cells. NK-cell self-tolerance is thought to be maintained by self-major histocompatibility complex (MHC) class I recognition; however, there are examples where NK cells are not regulated by MHC class I and yet remain self-tolerant. Here, we show that 2B4 (CD244) and CD48 represent a second system for murine NK-cell self-recognition. 2B4 and MHC class I receptors act nonredundantly to inhibit NK lysis of syngeneic tumor cells. NK cells from beta2 microglobulin (beta2m)-deficient mice and NK cells that lack expression of self-MHC-binding inhibitory receptors are inhibited by 2B4. Moreover, we provide the first in vivo evidence for MHC-independent NK self-recognition in a bone marrow rejection assay. These data suggest that NK-cell self-tolerance can be mediated by molecules other than MHC.

MeSH Terms
Animals Antigens, CD/immunology Bone Marrow Transplantation/immunology CD48 Antigen Cytotoxicity, Immunologic Graft Rejection/immunology Histocompatibility Antigens Class I/immunology Killer Cells, Natural/immunology Membrane Glycoproteins/immunology Mice Mice, Knockout Neoplasms/immunology,pathology Receptors, Immunologic/immunology Self Tolerance Signaling Lymphocytic Activation Molecule Family Transplantation, Isogeneic beta 2-Microglobulin/deficiency
Chemicals
Antigens, CD CD48 Antigen Cd244a protein, mouse Cd48 protein, mouse Histocompatibility Antigens Class I Membrane Glycoproteins Receptors, Immunologic Signaling Lymphocytic Activation Molecule Family beta 2-Microglobulin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
McNerney Megan E
Department of Pathology, University of Chicago, 5841 S Maryland Ave, S-315 MC3083, Chicago, IL 60637, USA. mcnerney@midway.uchicago.edu
Guzior Dustin
Kumar Vinay
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2005-01-0357
Email
mcnerney@midway.uchicago.edu
Published
2005-08-15
Epub
2005-00-03
Pages
1337-40
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895194
Subset
IM
Grants
NIGMS NIH HHS · GM07281 · United States
NIAID NIH HHS · R01AI20451 · United States
External Links
PubMed source DOI: 10.1182/blood-2005-01-0357 PMC Full Text View journal details
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