The Experts below are selected from a list of 1257 Experts worldwide ranked by ideXlab platform
Mitchell Kronenberg - One of the best experts on this subject based on the ideXlab platform.
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ICOS costimulates invariant NKT cell activation
Biochemical and biophysical research communications, 2005Co-Authors: Hiroshi Kaneda, Mitchell Kronenberg, Yoshinori Ikarashi, Kazuyoshi Takeda, Tsuyoshi Ota, Yuki Kaduka, Hisaya Akiba, Hiro Wakasugi, Katsuyuki Kinoshita, Hideo YagitaAbstract:It has been reported that costimulatory molecules, CD80/86-CD28 and CD154-CD40, critically contribute to activation of CD1d-restricted invariant NKT (iNKT) cells. Here we have demonstrated that ICOS, a new member of the CD28 family, plays a substantial role in iNKT cell activation. iNKT cells constitutively expressed ICOS as well as CD28 independently, and ICOS expression was further up-regulated 2-3 days after Alpha-Galactosylceramide (Alpha-GalCer) treatment. Blockade of ICOS-mediated costimulation by administration of anti-ICOS ligand (B7RP-1) mAb or by ICOS gene knockout substantially inhibited Alpha-GalCer-induced IFN-gamma and IL-4 production, cytotoxic activity, and anti-metastatic effect. Moreover, blockade of both B7RP-1-ICOS and CD80/86-CD28 interactions mostly abolished the Alpha-GalCer-induced immune responses. These findings indicate that iNKT cell activation is regulated by CD28 and IOCS independently.
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surprisingly minor influence of trav11 vAlpha14 polymorphism on nk t receptor mcd1 Alpha Galactosylceramide binding kinetics
Immunogenetics, 2003Co-Authors: Bee-cheng Sim, Kaisa Holmberg, Stephane Sidobre, Olga Naidenko, Nathalie Niederberger, Shane D. Marine, Mitchell KronenbergAbstract:Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) Alpha-chain locus "c" (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an "invariant" TRAV11J15 (previously called AV14J18 or VAlpha14 JAlpha281) Alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid Alpha-Galactosylceramide (Alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in Alpha-chain J-region usage or in the CDR3Alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/Alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains.
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Surprisingly minor influence of TRAV11 (VAlpha14) polymorphism on NK T-receptor mCD1/Alpha-Galactosylceramide binding kinetics.
Immunogenetics, 2003Co-Authors: Bee-cheng Sim, Mitchell Kronenberg, Kaisa Holmberg, Stephane Sidobre, Olga Naidenko, Nathalie Niederberger, Shane D. Marine, Nicholas R. J. GascoigneAbstract:Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) Alpha-chain locus "c" (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an "invariant" TRAV11J15 (previously called AV14J18 or VAlpha14 JAlpha281) Alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid Alpha-Galactosylceramide (Alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in Alpha-chain J-region usage or in the CDR3Alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/Alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains.
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prolonged ifn gamma producing nkt response induced with Alpha Galactosylceramide loaded dcs
Nature Immunology, 2002Co-Authors: Shinichiro Fujii, Kanako Shimizu, Mitchell Kronenberg, Ralph M SteinmanAbstract:Natural killer T (NKT) lymphocytes mediate a rapid reaction to the glycolipid drug Alpha-Galactosylceramide (Alpha GalCer), which triggers release of large amounts of cytokines into the serum within 12 h, starting with interleukin 4 (IL-4). When Alpha GalCer is administered to mice on dendritic cells (DCs) instead, the response is more prolonged (>4 days) and marked by a large expansion in IFN-gamma-producing NKT cells as well as greater resistance to metastases of the B16 melanoma. Nevertheless, DCs from mice given free Alpha GalCer are able to induce strong IFN-gamma-producing NKT responses when transferred to naive mice, but not when transferred to Alpha GalCer-treated recipients. In the latter, the NKT cells are energized and can respond to glycolipid only in the presence of supplemental IL-2. Therefore, when Alpha GalCer is selectively targeted to DCs, mice develop a stronger, more prolonged and effector type of NKT response, but this response can be blocked by the induction of anergy after presentation of Alpha GalCer on other cells.
Bee-cheng Sim - One of the best experts on this subject based on the ideXlab platform.
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Surprisingly minor influence of TRAV11 (VAlpha14) polymorphism on NK T-receptor mCD1/Alpha-Galactosylceramide binding kinetics.
Immunogenetics, 2003Co-Authors: Bee-cheng Sim, Mitchell Kronenberg, Kaisa Holmberg, Stephane Sidobre, Olga Naidenko, Nathalie Niederberger, Shane D. Marine, Nicholas R. J. GascoigneAbstract:Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) Alpha-chain locus "c" (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an "invariant" TRAV11J15 (previously called AV14J18 or VAlpha14 JAlpha281) Alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid Alpha-Galactosylceramide (Alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in Alpha-chain J-region usage or in the CDR3Alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/Alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains.
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surprisingly minor influence of trav11 vAlpha14 polymorphism on nk t receptor mcd1 Alpha Galactosylceramide binding kinetics
Immunogenetics, 2003Co-Authors: Bee-cheng Sim, Kaisa Holmberg, Stephane Sidobre, Olga Naidenko, Nathalie Niederberger, Shane D. Marine, Mitchell KronenbergAbstract:Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) Alpha-chain locus "c" (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an "invariant" TRAV11J15 (previously called AV14J18 or VAlpha14 JAlpha281) Alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid Alpha-Galactosylceramide (Alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in Alpha-chain J-region usage or in the CDR3Alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/Alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains.
Olga Naidenko - One of the best experts on this subject based on the ideXlab platform.
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Surprisingly minor influence of TRAV11 (VAlpha14) polymorphism on NK T-receptor mCD1/Alpha-Galactosylceramide binding kinetics.
Immunogenetics, 2003Co-Authors: Bee-cheng Sim, Mitchell Kronenberg, Kaisa Holmberg, Stephane Sidobre, Olga Naidenko, Nathalie Niederberger, Shane D. Marine, Nicholas R. J. GascoigneAbstract:Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) Alpha-chain locus "c" (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an "invariant" TRAV11J15 (previously called AV14J18 or VAlpha14 JAlpha281) Alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid Alpha-Galactosylceramide (Alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in Alpha-chain J-region usage or in the CDR3Alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/Alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains.
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surprisingly minor influence of trav11 vAlpha14 polymorphism on nk t receptor mcd1 Alpha Galactosylceramide binding kinetics
Immunogenetics, 2003Co-Authors: Bee-cheng Sim, Kaisa Holmberg, Stephane Sidobre, Olga Naidenko, Nathalie Niederberger, Shane D. Marine, Mitchell KronenbergAbstract:Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) Alpha-chain locus "c" (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an "invariant" TRAV11J15 (previously called AV14J18 or VAlpha14 JAlpha281) Alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid Alpha-Galactosylceramide (Alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in Alpha-chain J-region usage or in the CDR3Alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/Alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains.
Shane D. Marine - One of the best experts on this subject based on the ideXlab platform.
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Surprisingly minor influence of TRAV11 (VAlpha14) polymorphism on NK T-receptor mCD1/Alpha-Galactosylceramide binding kinetics.
Immunogenetics, 2003Co-Authors: Bee-cheng Sim, Mitchell Kronenberg, Kaisa Holmberg, Stephane Sidobre, Olga Naidenko, Nathalie Niederberger, Shane D. Marine, Nicholas R. J. GascoigneAbstract:Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) Alpha-chain locus "c" (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an "invariant" TRAV11J15 (previously called AV14J18 or VAlpha14 JAlpha281) Alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid Alpha-Galactosylceramide (Alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in Alpha-chain J-region usage or in the CDR3Alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/Alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains.
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surprisingly minor influence of trav11 vAlpha14 polymorphism on nk t receptor mcd1 Alpha Galactosylceramide binding kinetics
Immunogenetics, 2003Co-Authors: Bee-cheng Sim, Kaisa Holmberg, Stephane Sidobre, Olga Naidenko, Nathalie Niederberger, Shane D. Marine, Mitchell KronenbergAbstract:Defects in natural killer T (NK T) cell function and of interleukin-4 -production in SJL and NOD mice have been linked to susceptibility to autoimmune disease. As SJL and NOD mice both carry the T-cell receptor (TCR) Alpha-chain locus "c" (Tcra(c)) haplotype, found in few other strains, we have attempted to determine the influence of Tcra polymorphism on NK T-cell recognition of ligand, selection, and immune responses. The majority of NK T cells use an "invariant" TRAV11J15 (previously called AV14J18 or VAlpha14 JAlpha281) Alpha- chain paired with either TRBV13-2, BV29, or BV1 to recognize ligands presented by mCD1 molecules, including the glycolipid Alpha-Galactosylceramide (Alpha-GalCer). Sequencing of TRAV11 from the mouse strains B10.A (encoding the Tcra(b) haplotype), B10.A- Tcra(c), and NOD (Tcra(c)) shows that Tcra(c) has a single TRAV11 gene (TRAV11*01) and that Tcra(b) has a single expressed gene (TRAV11*02), plus a closely related pseudogene. There is no apparent difference in Alpha-chain J-region usage or in the CDR3Alpha sequence at the TRAV11-J15 junction between the haplotypes in TRAV11-bearing NK T cells. Using Biacore and tetramer-binding and decay assays, we have determined that the interaction between Tcra(c) TRAV11*01 NK T TCR and the mCD1/Alpha-GalCer complex is slightly weaker than that of Tcra(b) (i.e., TRAV11*02) NK T TCR. These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains.
Jagannadha K Sastry - One of the best experts on this subject based on the ideXlab platform.
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enhancement of mucosal immunogenicity of viral vectored vaccines by the nkt cell agonist Alpha Galactosylceramide as adjuvant
Vaccine, 2014Co-Authors: Shailbala Singh, Pramod N Nehete, Bharti P Nehete, Guojun Yang, Patrick W Hanley, Michael A Barry, Jagannadha K SastryAbstract:Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of Alpha-Galactosylceramide (α-GalCer), a synthetic glycolipid agonist of natural killer T (NKT) cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.
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Nanoparticle formulated Alpha-Galactosylceramide activates NKT cells without inducing anergy.
Vaccine, 2009Co-Authors: Prakash Thapa, Chengfeng Xia, Guodong Zhang, Alexander Gelbard, Willem W Overwijk, Chengwen Liu, Patrick Hwu, David Z Chang, Amy Courtney, Jagannadha K SastryAbstract:Activation of innate immunity is critical for vaccine development and immunotherapy, through triggering antigen specific immune responses. Natural killer T (NKT) cells are a unique type of innate immune cells which exert potent anti-viral and anti-metastasis function, through producing interferon-gamma and activating dendritic cells to present tumor antigens to CD8 T cells. Alpha-Galactosylceramide, a synthetic antigen for NKT cells, is an adjuvant for protein antigens which can induce protective immunity against cancer and viral diseases, and has been proven to be safe and immune stimulatory in human cancer and hepatitis patients. Current existing problem for Alpha-Galactosylceramide is its induction of anergy of NKT cells, due to the non-selective presentation of Alpha-Galactosylceramide antigen by B cells. We hypothesized that nanoparticle formulated Alpha-Galactosylceramide may be selectively presented by dendritic cells and macrophages, but not B cells, thus avoiding anergy induction in NKT cells. We have prepared poly-lactic acid based nanoparticles conjugated with Alpha-Galactosylceramide, examined their stimulation of NKT cells in vitro and in vivo in mice, and showed that nanoparticle formulated Alpha-Galactosylceramide stimulates NKT cells. In contrast to soluble Alpha-Galactosylceramide, which caused NKT anergy after single stimulation, nanoparticle formulated Alpha-Galactosylceramide repeatedly stimulates NKT cells without inducing anergy. Mechanistic studies showed that nanoparticle formulated Alpha-Galactosylceramide is efficiently presented by mouse CD11c+population containing dendritic cells, and CD11b+population containing macrophages, but very poorly by B220+population containing B cells. Hence, nanoparticle formulated Alpha-Galactosylceramide is an attractive immunomodulator for immunotherapy and vaccine development. Future studies will be focused on its application as adjuvant for protein and/or peptide antigens.