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PMID: 15728129 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules.

Blood ·Vol. 105 ·No. 11 ·2005-06-01 ·Pages 4416-23

Fernandez NC, Treiner E, Vance RE, Jamieson AM, Lemieux S, Raulet DH

Abstract

It is widely believed that self-tolerance of natural killer (NK) cells occurs because each NK cell expresses at least one inhibitory receptor specific for a host major histocompatibility complex (MHC) class I molecule. Here we report that some NK cells lack all known self-MHC-specific inhibitory receptors, yet are nevertheless self-tolerant. These NK cells exhibit a normal cell surface phenotype and some functional activity. However, they respond poorly to class I-deficient normal cells, tumor cells, or cross-linking of stimulatory receptors, suggesting that self-tolerance is established by dampening stimulatory signaling. Thus, self-tolerance of NK cells in normal animals can occur independently of MHC-mediated inhibition, and hyporesponsiveness plays a role in self-tolerance of NK cells, as also proposed for B and T cells.

MeSH Terms
Animals Histocompatibility Antigens/immunology Immunophenotyping Killer Cells, Natural/cytology,immunology Lymphocyte Subsets Mice Mice, Inbred Strains Mice, Knockout Receptors, Immunologic/analysis Self Tolerance/immunology Signal Transduction/immunology
Chemicals
Histocompatibility Antigens Receptors, Immunologic
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fernandez Nadine C
Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
Treiner Emmanuel
Vance Russell E
Jamieson Amanda M
Lemieux Suzanne
Raulet David H
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2004-08-3156
Published
2005-06-01
Epub
2005-00-22
Pages
4416-23
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895026
Subset
IM
Grants
NIAID NIH HHS · R01-AI35021 · United States
External Links
PubMed source DOI: 10.1182/blood-2004-08-3156 PMC Full Text View journal details
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