A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules.
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.
Fernandez
Nadine C
NC
Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
Treiner
Emmanuel
E
Vance
Russell E
RE
Jamieson
Amanda M
AM
Lemieux
Suzanne
S
Raulet
David H
DH
D000818:Animals; D006649:Histocompatibility Antigens / Q000276:immunology*; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology*; D016131:Lymphocyte Subsets; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000032:analysis*; D017634:Self Tolerance / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D006649:Histocompatibility Antigens; D011971:Receptors, Immunologic
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