The Murine Nonclassical Class I Major Histocompatibility Complex–like CD1.1 Molecule Protects Target Cells from Lymphokine-activated Killer Cell Cytolysis

Chang, Chew Shun; Brossay, Laurent; Kronenberg, Mitchell; Kane, Kevin P.

doi:10.1084/jem.189.3.483

Cited by 37 publications

(44 citation statements)

References 57 publications

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“…Expression of MHC-Ib molecules such as Qa-1 b , H-2 Blastocyst , CD1d, and Q9 have all been shown to inhibit NK-cell cytotoxicity. [29][30][31][32] However, only one inhibitory receptor for Qa-1 b has been identified (NKG2A). 33 The ligand for KLRI is unknown, but the structural and primary homology to the NKG2 family suggests that KLRI ligands may also be MHC-Ib proteins.…”

Section: Discussionmentioning

confidence: 99%

Impaired natural killer cell self-education and “missing-self” responses in Ly49-deficient mice

Bélanger

Rahim

et al. 2012

Blood

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Ly49-mediated recognition of MHC-I molecules on host cells is considered vital for natural killer (NK)–cell regulation and education; however, gene-deficient animal models are lacking because of the difficulty in deleting this large multigene family. Here, we describe NK gene complex knockdown (NKCKD) mice that lack expression of Ly49 and related MHC-I receptors on most NK cells. NKCKD NK cells exhibit defective killing of MHC-I–deficient, but otherwise normal, target cells, resulting in defective rejection by NKCKD mice of transplants from various types of MHC-I–deficient mice. Self–MHC-I immunosurveillance by NK cells in NKCKD mice can be rescued by self–MHC-I–specific Ly49 transgenes. Although NKCKD mice display defective recognition of MHC-I–deficient tumor cells, resulting in decreased in vivo tumor cell clearance, NKG2D- or antibody-dependent cell-mediated cytotoxicity–induced tumor cell cytotoxicity and cytokine production induced by activation receptors was efficient in Ly49-deficient NK cells, suggesting MHC-I education of NK cells is a single facet regulating their total potential. These results provide direct genetic evidence that Ly49 expression is necessary for NK-cell education to self–MHC-I molecules and that the absence of these receptors leads to loss of MHC-I–dependent “missing-self” immunosurveillance by NK cells.

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Section: Discussionmentioning

confidence: 99%

Impaired natural killer cell self-education and “missing-self” responses in Ly49-deficient mice

Bélanger

Rahim

et al. 2012

Blood

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“…Infected iDCs up-regulate the expression of CD1d on the cell surface. Expression of CD1a, b, and c molecules (32) as well as CD1d (26,27) can protect MHC class I-negative target cells from NK-mediated cytolysis. In this case, the expression of CD1d does not confer a significant degree of protection as shown in our blocking experiments using anti-CD1d Abs.…”

Section: Discussionmentioning

confidence: 99%

Immature Human Dendritic Cells Infected with Leishmania infantum Are Resistant to NK-Mediated Cytolysis but Are Efficiently Recognized by NKT Cells

Campos-Martín

Colmenares

Gozalbo-López

et al. 2006

The Journal of Immunology

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Dendritic cells (DC) play an important role in innate and adaptive immunity, interacting with T cells, NK, and NKT cells. A critical step in the interaction of the parasitic protozoa Leishmania with their host is the evasion of both innate and adaptive immunity, producing a long-lasting chronic infection. There is growing evidence that these parasites can modify the Ag-presenting and immunoregulatory functions of DCs. The cells and mechanisms involved in innate immune response against Leishmania are still poorly understood. In this study, we investigated how Leishmania infantum infection affects DC interactions with NK and invariant NKT (iNKTs) cells in humans. We found that infected immature DCs (iDCs) do not up-regulate HLA class I molecules. Despite this, iDCs become resistant to killing mediated by autologous NK cells due to the up-regulation of HLA-E expression, which protects target cells from NK-mediated lysis through interaction with the inhibitory receptor CD94/NKG2A. Furthermore, iDCs infected with L. infantum up-regulate CD1d cell surface expression and consequently can be efficiently recognized and killed by iNKT cells that produce IFN-γ. These data suggest that L. infantum could be able to evade NK recognition; in contrast, iNKTs may play an important role in the immune response against Leishmania.

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“…WT1-nonexpressing P815 cells with nonidentical H-2 molecules were not lysed by the CTLs (data not shown). RMAS cells that were common targets for lymphokine-activated killer/NK cells (31) were not killed by the CTLs (Fig. 3a).…”

Section: Lysis Of Endogenously Wt1-expressing Tumor Cells By Db126-spmentioning

confidence: 99%

Cancer Immunotherapy Targeting Wilms’ Tumor Gene WT1 Product

Oka¹,

Udaka

Tsuboi³

et al. 2000

The Journal of Immunology

187

157

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The Wilms’ tumor gene WT1 is expressed at high levels not only in acute myelocytic and lymphocytic leukemia and in chronic myelocytic leukemia but also in various types of solid tumors including lung cancers. To determine whether the WT1 protein can serve as a target Ag for tumor-specific immunity, three 9-mer WT1 peptides (Db126, Db221, and Db235), which contain H-2Db-binding anchor motifs and have a comparatively higher binding affinity for H-2Db molecules, were tested in mice (C57BL/6, H-2Db) for in vivo induction of CTLs directed against these WT1 peptides. Only one peptide, Db126, with the highest binding affinity for H-2Db molecules induced vigorous CTL responses. The CTLs specifically lysed not only Db126-pulsed target cells dependently upon Db126 concentrations but also WT1-expressing tumor cells in an H-2Db-restricted manner. The sensitizing activity to the Db126-specific CTLs was recovered from the cell extract of WT1-expressing tumor cells targeted by the CTLs in the same retention time as that needed for the synthetic Db126 peptide in RP-HPLC, indicating that the Db126-specific CTLs recognize the Db126 peptide to kill WT1-expressing target cells. Furthermore, mice immunized with the Db126 peptide rejected challenges by WT1-expressing tumor cells and survived for a long time with no signs of autoaggression by the CTLs. Thus, the WT1 protein was identified as a novel tumor Ag. Immunotherapy targeting the WT1 protein should find clinical application for various types of human cancers.

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The Murine Nonclassical Class I Major Histocompatibility Complex–like CD1.1 Molecule Protects Target Cells from Lymphokine-activated Killer Cell Cytolysis

Cited by 37 publications

References 57 publications

Impaired natural killer cell self-education and “missing-self” responses in Ly49-deficient mice

Impaired natural killer cell self-education and “missing-self” responses in Ly49-deficient mice

Immature Human Dendritic Cells Infected with Leishmania infantum Are Resistant to NK-Mediated Cytolysis but Are Efficiently Recognized by NKT Cells

Cancer Immunotherapy Targeting Wilms’ Tumor Gene WT1 Product

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