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

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.

SUBMITTER: Fernandez NC

PROVIDER: S-EPMC1895026 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature

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

Fernandez Nadine C NC Treiner Emmanuel E Vance Russell E RE Jamieson Amanda M AM Lemieux Suzanne S Raulet David H DH

Blood 20050222 11

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 c ...[more]

PMID: 15728129

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2020-06-05 | GSE147596 | GEO

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| S-EPMC8896794 | biostudies-literature

Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation.

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Natural killer cell tolerance persists despite significant reduction of self MHC class I on normal target cells in mice.

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A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature.

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