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Blood. 2005 Jun 1;105(11):4416-23. Epub 2005 Feb 22.

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

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  • 1Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.


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.

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