Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Curr Protoc Immunol ; 131(1): e111, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33147370

RESUMO

Cellular interactions are often essential to regulate immune cell activities during an immune response. To understand the details of this process, it is necessary to study individual receptor/ligand interactions in a quantitative fashion. However, this is often very difficult or even impossible when using real cells for stimulation. Here, we present a method to use cell-sized latex beads for such studies. These beads can be coated with agonistic antibodies or specific ligands in a defined and quantifiable fashion. This creates the possibility of titrating the strength of the stimulation for a specific receptor in a three-dimensional system. Using natural killer (NK) cells as an example, we demonstrate how these beads can be used to stimulate NK cell responses. © 2020 The Authors. Basic Protocol 1: Covalent coating of latex beads with antibodies Basic Protocol 2: Quantification of the amount of antibodies on the beads with the QIFIKIT® Alternate Protocol 1: Covalent coating of latex beads with streptavidin to bind biotinylated proteins Alternate Protocol 2: Quantification of the amount of protein on the beads with the QIFIKIT® Support Protocol: Functional testing of the beads in a natural killer cell degranulation assay.

2.
Eur J Immunol ; 50(5): 656-665, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32027754

RESUMO

Natural Killer (NK) cell responses are regulated by a variety of different surface receptors. While we can determine the overall positive or negative effect of a given receptor on NK cell functions, investigating NK cell regulation in a quantitative way is challenging. To quantitatively investigate individual receptors for their effect on NK cell activation, we chose to functionalize latex beads that have approximately the same size as lymphocytes with defined amounts of specific antibodies directed against distinct activating receptors. This enabled us to investigate NK cell reactivity in a defined, clean, and controllable system. Only CD16 and NKp30 could activate the degranulation of resting human NK cells. CD16, NKG2D, NKp30, NKp44, and NKp46 were able to activate cultured NK cells. NK cell activation resulted in the induction of polyfunctional cells that degranulated and produced IFN-γ and MIP-1ß. Interestingly, polyfunctional NK cells were only induced by triggering ITAM-coupled receptors. NKp44 showed a very sensitive response pattern, where a small increase in receptor stimulation caused maximal NK cell activity. In contrast, stimulation of 2B4 induced very little NK cell degranulation, while providing sufficient signal for NK cell adhesion. Our data demonstrate that activating receptors differ in their effectiveness to stimulate NK cells.


Assuntos
Anticorpos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Anticorpos/química , Adesão Celular/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Células Cultivadas , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Humanos , Interferon gama/genética , Interferon gama/imunologia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Microesferas , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Receptor 1 Desencadeador da Citotoxicidade Natural/genética , Receptor 1 Desencadeador da Citotoxicidade Natural/imunologia , Receptor 2 Desencadeador da Citotoxicidade Natural/genética , Receptor 2 Desencadeador da Citotoxicidade Natural/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/genética , Receptor 3 Desencadeador da Citotoxicidade Natural/imunologia , Ligação Proteica , Receptores de IgG/genética , Receptores de IgG/imunologia , Transdução de Sinais
3.
Cell Mol Immunol ; 17(4): 347-355, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31471588

RESUMO

Natural killer (NK) cells participate in early immune defenses against pathogens and tumors and play a major role as immune effector and regulatory cells. The NK cell-mediated elimination of an infected or cancerous cell is a highly regulated process that requires the formation of a cell contact, the establishment of an immunological synapse and the polarization and release of lytic granules. Additionally, the detachment of NK cells from target cells is important for NK cells to bind and kill other cells in a process called serial killing. However, very little is known about this detachment process. Here, we show that NK detachment is directly connected to the successful killing of a target cell. The inhibition of killing due to reduced NK cell cytotoxicity or increased target cell resistance results in defective detachment and prolonged contact times. This effect leads to sustained Ca2+ flux in NK cells and the hypersecretion of proinflammatory cytokines. Linking defective cytotoxicity with enhanced cytokine secretion via reduced detachment may explain inflammatory pathologies in several diseases.

4.
Arthritis Res Ther ; 21(1): 277, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829278

RESUMO

OBJECTIVE: In the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab's mechanism of action in GPA. METHODS: B cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry. RESULTS: NK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions. CONCLUSION: B cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab's mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies.


Assuntos
Granulomatose com Poliangiite/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Células Matadoras Naturais/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Rituximab/uso terapêutico , Granulomatose com Poliangiite/imunologia , Humanos , Células Matadoras Naturais/imunologia
5.
J Exp Med ; 216(9): 2113-2127, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31270246

RESUMO

NK cells eliminate virus-infected and tumor cells by releasing cytotoxic granules containing granzyme B (GrzB) or by engaging death receptors that initiate caspase cascades. The orchestrated interplay between both cell death pathways remains poorly defined. Here we simultaneously measure the activities of GrzB and caspase-8 in tumor cells upon contact with human NK cells. We observed that NK cells switch from inducing a fast GrzB-mediated cell death in their first killing events to a slow death receptor-mediated killing during subsequent tumor cell encounters. Target cell contact reduced intracellular GrzB and perforin and increased surface-CD95L in NK cells over time, showing how the switch in cytotoxicity pathways is controlled. Without perforin, NK cells were unable to perform GrzB-mediated serial killing and only killed once via death receptors. In contrast, the absence of CD95 on tumor targets did not impair GrzB-mediated serial killing. This demonstrates that GrzB and death receptor-mediated cytotoxicity are differentially regulated during NK cell serial killing.


Assuntos
Citotoxicidade Imunológica , Granzimas/metabolismo , Células Matadoras Naturais/imunologia , Receptores de Morte Celular/metabolismo , Caspase 8/metabolismo , Células HeLa , Humanos , Cinética , Perforina/metabolismo , Receptor fas/metabolismo
6.
Clin Immunol ; 204: 37-42, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30359773

RESUMO

SLAM family receptors are important for the fine-tuning of immune reactions. Their expression is restricted to cells of hematopoietic origin and most SLAM family receptors are their own ligand. Here we review how these receptors are involved in regulating the functions of Natural Killer (NK) cells. We discuss that promoting cellular adhesion may be a main function of SLAM family receptors in NK cells. The homophilic interactions of SLAM family receptors can not only occur in trans between different cells, but also in cis on the surface of the same cell. This cis interaction additionally modulates the function of the receptors and subsequently affects the activities of NK cells. Finally, SLAM-family receptors can also mediate inhibitory signals under certain conditions. These inhibitory signals can contribute to the functional maturation of NK cells during NK cell education. Therefore, SLAM family receptors are critically involved in many aspects of NK cell functionality.


Assuntos
Adesão Celular/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Família de Moléculas de Sinalização da Ativação Linfocitária/imunologia , Animais , Humanos
7.
Front Immunol ; 9: 1840, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30135688

RESUMO

Natural killer (NK) cells eliminate infected and tumorigenic cells through delivery of granzymes via perforin pores or by activation of caspases via death receptors. In order to understand how NK cells combine different cell death mechanisms, it is important to quantify target cell responses on a single cell level. However, currently existing reporters do not allow the measurement of several protease activities inside the same cell. Here, we present a strategy for the comparison of two different proteases at a time inside individual target cells upon engagement by NK cells. We developed single-fluorescent protein reporters containing the RIEAD or the VGPD cleavage site for the measurement of granzyme B activity. We show that these two granzyme B reporters can be applied in combination with caspase-8 or caspase-3 reporters. While we did not find that caspase-8 was activated by granzyme B, our method revealed that caspase-3 activity follows granzyme B activity with a delay of about 6 min. Finally, we illustrate the comparison of several different reporters for granzyme A, M, K, and H. The approach presented here is a valuable means for the investigation of the temporal evolution of cell death mediated by cytotoxic lymphocytes.


Assuntos
Caspases/metabolismo , Expressão Gênica , Genes Reporter , Granzimas/metabolismo , Células Matadoras Naturais/metabolismo , Apoptose , Morte Celular , Humanos , Células Matadoras Naturais/imunologia , Proteólise , Análise de Célula Única
8.
J Immunol ; 198(5): 1944-1951, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28100681

RESUMO

The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The binding affinity and avidity of integrins can be regulated via inside-out signals from other receptors. In this article, we investigate the signals necessary to activate LFA-1 in human NK cells. Our data show that LFA-1 has a low ligand-binding activity in resting human NK cells, but it can be stimulated by triggering activating receptors, such as 2B4 or CD16, or by coactivation of different receptor combinations. Short-term stimulation of freshly isolated NK cells with cytokines, such as IL-15, IL-12, or IL-18, does not activate LFA-1 but increases the responsiveness of the cells to subsequent receptor stimulation. Different NK cell subsets vary in their ability to induce LFA-1 binding activity after activating receptor stimulation. Interestingly, the NK cell subsets that are more mature and possess higher cytotoxic potential also show the highest activation of LFA-1, which correlated with the expression of the small calcium-binding protein S100A4. Our data suggest that regulation of LFA-1 is one reason for the different activity of NK cells during differentiation.


Assuntos
Diferenciação Celular , Citocinas/imunologia , Células Matadoras Naturais/fisiologia , Antígeno-1 Associado à Função Linfocitária/imunologia , Antígeno-1 Associado à Função Linfocitária/metabolismo , Transdução de Sinais , Proteínas de Transporte/imunologia , Citocinas/genética , Citotoxicidade Imunológica , Proteínas Ligadas por GPI/imunologia , Regulação da Expressão Gênica , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-15/genética , Interleucina-15/imunologia , Interleucina-18/genética , Interleucina-18/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Antígeno-1 Associado à Função Linfocitária/genética , Receptores de IgG/imunologia
9.
J Toxicol Environ Health A ; 79(22-23): 1078-1084, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27924718

RESUMO

Natural killer (NK) cells are important immune effector cells that protect the organism against viral infections and cancer. The cytotoxic activity of NK cells is induced by the engagement of a number of different activating surface receptors and controlled by inhibitory receptors to ensure self-tolerance. Resting NK cells need to be co-activated by involvement of at least two distinct activating receptors in order to induce their functional activity. However, in cultured NK cells, which have been expanded in cytokines such as interleukin (IL)-2, the engagement of a single activating receptor may be sufficient to induce their function. Data demonstrated that also cultured NK cells may be co-activated by involvement of certain combinations of activating receptors. This co-activation results in enhanced activation of Vav-1 and ERK signaling pathways and produces greater degranulation. In addition to enhanced functionality, co-activation makes NK cells more resistant to the effect of inhibitory receptors, thereby inducing more potent and efficient NK cell responses.


Assuntos
Células Matadoras Naturais/metabolismo , Sistema de Sinalização das MAP Quinases , Receptores de Células Matadoras Naturais/genética , Humanos , Fosforilação , Proteínas Proto-Oncogênicas c-vav/metabolismo , Receptores de Células Matadoras Naturais/metabolismo , Transdução de Sinais
10.
Eur J Immunol ; 45(7): 2134-42, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25824372

RESUMO

Carcinoembryonicantigen-related cell adhesion molecule 1 (CEACAM1) is a receptor involved in the regulation of NK-cell function. In most species, the CEACAM1 cytoplasmic tail possesses a membrane-proximal ITIM paired with a membrane-distal immunoreceptor tyrosine-based switch motif (ITSM) signaling motif. Human CEACAM1 has phylogenetically relatively recently acquired a second ITIM instead of the ITSM and was shown to inhibit NKG2D-mediated NK-cell activation. Here, we compare the function of bovine and human CEACAM1. We show that in addition to NKG2D, human CEACAM1 can inhibit NK-cell activation via NKp30 or 2B4. Bovine CEACAM1, possessing an ITIM and an ITSM signaling motif, is also inhibitory. However, bovine CEACAM1 inhibition of NKp30-mediated lysis is less pronounced compared with its human counterpart. Bovine CEACAM1 inhibition is dependent on the membrane-proximal ITIM and our data suggest that also the membrane distal ITSM motif contributes to inhibitory signaling. Biochemically, human and bovine CEACAM1 can recruit the phosphatases SHP-1 and SHP-2 after receptor phosphorylation to a similar extend. Bovine CEACAM1 can additionally recruit the adapter molecule Ewing's sarcoma virus-activated transcript-2 (EAT-2), but not SLAM-associated protein (SAP). Taken together, we show that although human and bovine CEACAM1 are differentially equipped with ITIM and ITSM motifs, both receptors can inhibit NKp30 and 2B4 activation of NK cells.


Assuntos
Antígenos CD/imunologia , Moléculas de Adesão Celular/imunologia , Evolução Molecular , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/imunologia , Receptores Imunológicos/imunologia , Animais , Western Blotting , Bovinos , Linhagem Celular , Humanos , Imunoprecipitação , Família de Moléculas de Sinalização da Ativação Linfocitária , Transfecção
11.
F1000Prime Rep ; 6: 87, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25374665

RESUMO

Natural killer (NK) cells are lymphocytes that are important for early and effective immune responses against infections and cancer. In the last 40 years, many receptors, their corresponding ligands and signaling pathways that regulate NK cell functions have been identified. However, we now know that additional processes, such as NK cell education, differentiation and also the formation of NK cell memory, have a great impact on the reactivity of these cells. Here, we summarize the current knowledge about these modulatory processes.

12.
Proc Natl Acad Sci U S A ; 110(50): E4884-93, 2013 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-24218549

RESUMO

The E3 transcription unit of human adenoviruses (Ads) encodes immunomodulatory proteins. Interestingly, the size and composition of the E3 region differs considerably among Ad species, suggesting that distinct sets of immunomodulatory E3 proteins may influence their interaction with the human host and the disease pattern. However, to date, only common immune evasion functions of species C E3 proteins have been described. Here we report on the immunomodulatory activity of a species D-specific E3 protein, E3/49K. Unlike all other E3 proteins that act on infected cells, E3/49K seems to target uninfected cells. Initially synthesized as an 80- to 100-kDa type I transmembrane protein, E3/49K is subsequently cleaved, with the large ectodomain (sec49K) secreted. We found that purified sec49K exhibits specific binding to lymphoid cell lines and all primary leukocytes, but not to fibroblasts or epithelial cells. Consistent with this binding profile and the molecular mass, the sec49K receptor was identified as the cell surface protein tyrosine phosphatase CD45. Antibody-blocking studies suggested that sec49K binds to the membrane proximal domains present in all CD45 isoforms. Functional studies showed that sec49K can suppress the activation and cytotoxicity of natural killer cells as well as the activation, signaling, and cytokine production of T cells. Thus, we have discovered an adenovirus protein that is actively secreted and describe immunomodulatory activities of an E3 protein uniquely expressed by a single Ad species.


Assuntos
Proteínas E3 de Adenovirus/metabolismo , Adenovírus Humanos/metabolismo , Imunomodulação/imunologia , Antígenos Comuns de Leucócito/metabolismo , Leucócitos/imunologia , Adenovírus Humanos/genética , Western Blotting , Linhagem Celular Tumoral , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Células HEK293 , Humanos , Imunoprecipitação , Leucócitos/metabolismo
13.
Front Immunol ; 3: 359, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23264774

RESUMO

The activity of natural killer (NK) cells is regulated by various processes including education/licensing, priming, integration of positive and negative signals through an array of activating and inhibitory receptors, and the development of memory-like functionality. These processes are often very complex due to the large number of different receptors and signaling pathways involved. Understanding these complex mechanisms is therefore a challenge, but is critical for understanding NK cell regulation. Mathematical approaches can facilitate the analysis and understanding of complex systems. Therefore, they may be instrumental for studies in NK cell biology. Here we provide a review of the different mathematical approaches to the analysis of NK cell signal integration, activation, proliferation, and the acquisition of inhibitory receptors. These studies show how mathematical methods can aid the analysis of NK cell regulation.

14.
Int J Cancer ; 131(6): E916-27, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22419518

RESUMO

As NK cell immunotherapy is still poorly successful, combinations with drugs enhancing NK cell activity are of major interest. NK large granular lymphocyte expansions associated with improved survival have been described under monotherapy with the Bcr-Abl/Src inhibitor dasatinib, which inhibits NK cell functions in vitro. As Src kinases play a major role in inhibitory and activating signaling pathways of NK cells, both outcomes appear plausible. To clarify these contradictory observations and potentially enable the use of dasatinib as adjuvant, we analyzed how clinically relevant doses promote NK cell effector functions. Polyclonal human NK cells were studied ex vivo. Functional outcomes assessed included conjugate formation, calcium flux, receptor regulation, cytokine production, degranulation, cytotoxicity, apoptosis induction and signal transduction. While dasatinib inhibits NK cell effector functions during functional assays, 24 hr pretreatment of NK cells followed by washout of dasatinib, led to dose-dependent enhancement of cytokine production, degranulation marker expression and cytotoxicity against selected lymphoma and leukemia cell lines. Mechanistically, this was neither due to an altered viability of NK cells nor increased NKG2D, LFA-1 or conjugate formation with target cells. Receptor proximal signaling events were inhibited. However, a slight time dependent enhancement of Vav phosphorylation was observed under certain circumstances. The shift in Vav phosphorylation level may be one major mechanism for NK cell activity enhancement induced by dasatinib. Our findings argue for a careful timing and dosing of dasatinib application during leukemia/lymphoma treatment to enhance NK cell immunotherapeutic efforts.


Assuntos
Citotoxicidade Imunológica/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Leucemia/imunologia , Linfoma/imunologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Tiazóis/farmacologia , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular Tumoral , Citocinas/biossíntese , Dasatinibe , Proteínas Ligadas por GPI/análise , Granzimas/biossíntese , Antígenos de Histocompatibilidade Classe I/análise , Humanos , Células Matadoras Naturais/imunologia , Leucemia/patologia , Linfoma/patologia , Proteína 1 de Membrana Associada ao Lisossomo/biossíntese , Proteína 2 de Membrana Associada ao Lisossomo/biossíntese , Subfamília K de Receptores Semelhantes a Lectina de Células NK/análise , Necrose , Receptores de IgG/análise
15.
Front Biosci (Landmark Ed) ; 17: 1418-32, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22201812

RESUMO

Natural Killer (NK) cells are important for early immune reactions against viral infections and cancer. They are regulated by a highly redundant system of different activating and inhibitory receptors. Here we summarize our current understanding about the regulation of these cells and describe how mathematical modeling and systems biology approaches can help to shed some light on the complex regulatory network that governs NK cell reactivity.


Assuntos
Células Matadoras Naturais/imunologia , Humanos , Ativação Linfocitária
16.
Sci Signal ; 4(175): ra36, 2011 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-21632469

RESUMO

Natural killer (NK) cells are effector cells of the immune system whose activation is carefully regulated by the interplay of signals from activating and inhibitory receptors. Signals from activating receptors induce phosphorylation of the guanine nucleotide exchange factor Vav1, whereas those from inhibitory receptors lead to the dephosphorylation of Vav1 by the Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). Here, we used mathematical modeling and experiments with NK cells to gain insight into this integration of positive and negative signals at a molecular level. Our data showed a switch-like regulation of Vav1 phosphorylation, the extent of which correlated with the cytotoxic activity of NK cells. Comparison of our experimental results with the predictions that we derived from an ensemble of 72 mathematical models showed that a physical association between Src family kinases and activating receptors on NK cells was essential to generate the cytotoxic response. Our data support a central role for Vav1 in determining the cytotoxic activity of NK cells and provide insight into the molecular mechanism of the integration of positive and negative signals during lymphocyte activation.


Assuntos
Células Matadoras Naturais/metabolismo , Ativação Linfocitária/imunologia , Modelos Biológicos , Proteínas Proto-Oncogênicas c-vav/metabolismo , Transdução de Sinais/imunologia , Animais , Western Blotting , Humanos , Imunoprecipitação , Cinética , Camundongos , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo
17.
J Immunol ; 178(9): 5606-11, 2007 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-17442943

RESUMO

NKG2D is an activating receptor expressed on all human NK cells and a subset of T cells. In cytolytic conjugates between NK cells and target cells expressing its ligand MHC class I chain-related gene A, NKG2D accumulates at the immunological synapse with GM1-rich microdomains. Furthermore, NKG2D is specifically recruited to detergent-resistant membrane fractions upon ligation. However, in the presence of a strong inhibitory stimulus, NKG2D-mediated cytotoxicity can be intercepted, and recruitment of NKG2D to the immunological synapse and detergent-resistant membrane fractions is blocked. Also, downstream phosphorylation of Vav-1 triggered by NKG2D ligation is circumvented by coengaging inhibitory receptors. Thus, we propose that one way in which inhibitory signaling can control NKG2D-mediated activation is by blocking its recruitment to GM1-rich membrane domains. The accumulation of activating NK cell receptors in GM1-rich microdomains may provide the necessary platform from which stimulatory signals can proceed.


Assuntos
Gangliosídeo G(M1)/metabolismo , Células Matadoras Naturais/imunologia , Microdomínios da Membrana/metabolismo , Receptores Imunológicos/metabolismo , Actinas/metabolismo , Células Cultivadas , Gangliosídeo G(M1)/análise , Humanos , Células Matadoras Naturais/química , Ativação Linfocitária , Microdomínios da Membrana/química , Subfamília K de Receptores Semelhantes a Lectina de Células NK , Fosforilação , Proteínas Proto-Oncogênicas c-vav/metabolismo , Receptores Imunológicos/análise , Receptores Imunológicos/antagonistas & inibidores , Receptores KIR2DL1 , Receptores de Células Matadoras Naturais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA