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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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Paired immunoglobulin-like receptors mediate innate memory to non-self MHC molecules

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2020-06-05 | GSE147596 | GEO

Abrogation of self-tolerance by misfolded self-antigens complexed with MHC class II molecules.

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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.

Project description:Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient ("missing self"). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR ("missing ligand"), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell-depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN-gamma and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell-derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome.

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Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors.

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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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Paired immunoglobulin-like receptors mediate innate memory to non-self MHC molecules

Project description:Paired immunoglobulin-like receptors mediate innate memory to non-self MHC molecules

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Control of Viral Infection by Natural Killer Cell Inhibitory Receptors.

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