The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Richard J Hodes - One of the best experts on this subject based on the ideXlab platform.
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downmodulation of tumor suppressor p53 by t cell receptor signaling is critical for Antigen specific cd4 t cell responses
Immunity, 2014Co-Authors: Masashi Watanabe, Kyung Duk Moon, Melanie S Vacchio, Karen S Hathcock, Richard J HodesAbstract:Summary Antigen Specificity is critical in immune response and requires integration of Antigen-specific signals with Antigen-nonspecific signals such as those provided by cytokines. The mechanism integrating these pathways is incompletely understood. We report here that Antigen-specific proliferative responses of CD4 + T cells required downmodulation of tumor suppressor p53. In the absence of T cell receptor (TCR) signal, IL-2 induced sustained increase in p53 protein, which prevented proliferative responses despite strong signaling through the IL-2 receptor. In contrast, TCR signaling resulted in early termination of p53 protein expression by decreasing p53 mRNA as well as strong transcriptional induction of the p53-regulating protein Mdm2. Downmodulation of p53 in response to Antigen stimulation was in fact critical for Antigen-specific T cell proliferation, and preventing p53 degradation by inhibiting Mdm2 resulted in sustained p53 protein and prevented Antigen-specific T cell proliferation. It is thus termination of p53 by TCR signaling that allows proliferative responses, enforcing Antigen Specificity.
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Downmodulation of Tumor Suppressor p53 by T Cell Receptor Signaling Is Critical for Antigen-Specific CD4 + T Cell Responses
Immunity, 2014Co-Authors: Masashi Watanabe, Kyung Duk Moon, Melanie S Vacchio, Karen S Hathcock, Richard J HodesAbstract:Summary Antigen Specificity is critical in immune response and requires integration of Antigen-specific signals with Antigen-nonspecific signals such as those provided by cytokines. The mechanism integrating these pathways is incompletely understood. We report here that Antigen-specific proliferative responses of CD4 + T cells required downmodulation of tumor suppressor p53. In the absence of T cell receptor (TCR) signal, IL-2 induced sustained increase in p53 protein, which prevented proliferative responses despite strong signaling through the IL-2 receptor. In contrast, TCR signaling resulted in early termination of p53 protein expression by decreasing p53 mRNA as well as strong transcriptional induction of the p53-regulating protein Mdm2. Downmodulation of p53 in response to Antigen stimulation was in fact critical for Antigen-specific T cell proliferation, and preventing p53 degradation by inhibiting Mdm2 resulted in sustained p53 protein and prevented Antigen-specific T cell proliferation. It is thus termination of p53 by TCR signaling that allows proliferative responses, enforcing Antigen Specificity.
Giulia Franzoni - One of the best experts on this subject based on the ideXlab platform.
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Proteome-wide screening reveals immunodominance in the CD8 T cell response against classical swine fever virus with Antigen-Specificity dependent on MHC class I haplotype expression
2016Co-Authors: Giulia Franzoni, Nitin V. Kurkure, Sabine E. Essler, Miriam Pedrera, Helen E. Everett, Kikki B. Bodman-smith, Helen R. Crooke, Simon P. GrahamAbstract:Vaccination with live attenuated classical swine fever virus (CSFV) vaccines induces a rapid onset of protection which has been associated with virus-specific CD8 T cell IFN-c responses. In this study, we assessed the Specificity of this response, by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. Synthetic peptides were pooled to represent each of the 12 CSFV proteins and used to stimulate PBMC from four pigs rendered immune to CSFV by C-strain vaccination and subsequently challenged with the virulent Brescia strain. Significant IFN-c expression by CD8 T cells, assessed by flow cytometry, was induced by peptide pools representing the core, E2, NS2, NS3 and NS5A proteins. Dissection of these Antigenic peptide pools indicated that, in each instance, a single discrete Antigenic peptide or pair of overlapping peptides was responsible for the IFN-c induction. Screening and titration of Antigenic peptides or truncated derivatives identified the following Antigenic regions: core241–255 PESRKKLEKALLAWA and NS31902–1912 VEYSFIFLDEY, or minimal length Antigenic peptides: E2996–1003 YEPRDSYF, NS21223–1230 STVTGIFL and NS5A3070– 3078 RVDNALLKF. The epitopes are highly conserved across CSFV strains and variable sequence divergence was observed with related pestiviruses. Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-a in addition to IFN-c. Finally, the variability in the Antigen-Specificity of these immunodominant CD8 T cell responses was confirmed to be associated with expression o
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proteome wide screening reveals immunodominance in the cd8 t cell response against classical swine fever virus with Antigen Specificity dependent on mhc class i haplotype expression
PLOS ONE, 2013Co-Authors: Giulia Franzoni, Nitin V. Kurkure, Sabine E. Essler, Miriam Pedrera, Helen E. Everett, Helen R. Crooke, K Bodmansmith, Simon P. GrahamAbstract:Vaccination with live attenuated classical swine fever virus (CSFV) vaccines induces a rapid onset of protection which has been associated with virus-specific CD8 T cell IFN-γ responses. In this study, we assessed the Specificity of this response, by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. Synthetic peptides were pooled to represent each of the 12 CSFV proteins and used to stimulate PBMC from four pigs rendered immune to CSFV by C-strain vaccination and subsequently challenged with the virulent Brescia strain. Significant IFN-γ expression by CD8 T cells, assessed by flow cytometry, was induced by peptide pools representing the core, E2, NS2, NS3 and NS5A proteins. Dissection of these Antigenic peptide pools indicated that, in each instance, a single discrete Antigenic peptide or pair of overlapping peptides was responsible for the IFN-γ induction. Screening and titration of Antigenic peptides or truncated derivatives identified the following Antigenic regions: core241–255 PESRKKLEKALLAWA and NS31902–1912 VEYSFIFLDEY, or minimal length Antigenic peptides: E2996–1003 YEPRDSYF, NS21223–1230 STVTGIFL and NS5A3070–3078 RVDNALLKF. The epitopes are highly conserved across CSFV strains and variable sequence divergence was observed with related pestiviruses. Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-α in addition to IFN-γ. Finally, the variability in the Antigen-Specificity of these immunodominant CD8 T cell responses was confirmed to be associated with expression of distinct MHC class I haplotypes. Moreover, recognition of NS21223–1230 STVTGIFL and NS31902–1912 VEYSFIFLDEY by a larger group of C-strain vaccinated animals showed that these peptides could be restricted by additional haplotypes. Thus the Antigenic regions and epitopes identified represent attractive targets for evaluation of their vaccine potential against CSFV.
Simon P. Graham - One of the best experts on this subject based on the ideXlab platform.
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Proteome-wide screening reveals immunodominance in the CD8 T cell response against classical swine fever virus with Antigen-Specificity dependent on MHC class I haplotype expression
2016Co-Authors: Giulia Franzoni, Nitin V. Kurkure, Sabine E. Essler, Miriam Pedrera, Helen E. Everett, Kikki B. Bodman-smith, Helen R. Crooke, Simon P. GrahamAbstract:Vaccination with live attenuated classical swine fever virus (CSFV) vaccines induces a rapid onset of protection which has been associated with virus-specific CD8 T cell IFN-c responses. In this study, we assessed the Specificity of this response, by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. Synthetic peptides were pooled to represent each of the 12 CSFV proteins and used to stimulate PBMC from four pigs rendered immune to CSFV by C-strain vaccination and subsequently challenged with the virulent Brescia strain. Significant IFN-c expression by CD8 T cells, assessed by flow cytometry, was induced by peptide pools representing the core, E2, NS2, NS3 and NS5A proteins. Dissection of these Antigenic peptide pools indicated that, in each instance, a single discrete Antigenic peptide or pair of overlapping peptides was responsible for the IFN-c induction. Screening and titration of Antigenic peptides or truncated derivatives identified the following Antigenic regions: core241–255 PESRKKLEKALLAWA and NS31902–1912 VEYSFIFLDEY, or minimal length Antigenic peptides: E2996–1003 YEPRDSYF, NS21223–1230 STVTGIFL and NS5A3070– 3078 RVDNALLKF. The epitopes are highly conserved across CSFV strains and variable sequence divergence was observed with related pestiviruses. Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-a in addition to IFN-c. Finally, the variability in the Antigen-Specificity of these immunodominant CD8 T cell responses was confirmed to be associated with expression o
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proteome wide screening reveals immunodominance in the cd8 t cell response against classical swine fever virus with Antigen Specificity dependent on mhc class i haplotype expression
PLOS ONE, 2013Co-Authors: Giulia Franzoni, Nitin V. Kurkure, Sabine E. Essler, Miriam Pedrera, Helen E. Everett, Helen R. Crooke, K Bodmansmith, Simon P. GrahamAbstract:Vaccination with live attenuated classical swine fever virus (CSFV) vaccines induces a rapid onset of protection which has been associated with virus-specific CD8 T cell IFN-γ responses. In this study, we assessed the Specificity of this response, by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. Synthetic peptides were pooled to represent each of the 12 CSFV proteins and used to stimulate PBMC from four pigs rendered immune to CSFV by C-strain vaccination and subsequently challenged with the virulent Brescia strain. Significant IFN-γ expression by CD8 T cells, assessed by flow cytometry, was induced by peptide pools representing the core, E2, NS2, NS3 and NS5A proteins. Dissection of these Antigenic peptide pools indicated that, in each instance, a single discrete Antigenic peptide or pair of overlapping peptides was responsible for the IFN-γ induction. Screening and titration of Antigenic peptides or truncated derivatives identified the following Antigenic regions: core241–255 PESRKKLEKALLAWA and NS31902–1912 VEYSFIFLDEY, or minimal length Antigenic peptides: E2996–1003 YEPRDSYF, NS21223–1230 STVTGIFL and NS5A3070–3078 RVDNALLKF. The epitopes are highly conserved across CSFV strains and variable sequence divergence was observed with related pestiviruses. Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-α in addition to IFN-γ. Finally, the variability in the Antigen-Specificity of these immunodominant CD8 T cell responses was confirmed to be associated with expression of distinct MHC class I haplotypes. Moreover, recognition of NS21223–1230 STVTGIFL and NS31902–1912 VEYSFIFLDEY by a larger group of C-strain vaccinated animals showed that these peptides could be restricted by additional haplotypes. Thus the Antigenic regions and epitopes identified represent attractive targets for evaluation of their vaccine potential against CSFV.
Masashi Watanabe - One of the best experts on this subject based on the ideXlab platform.
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downmodulation of tumor suppressor p53 by t cell receptor signaling is critical for Antigen specific cd4 t cell responses
Immunity, 2014Co-Authors: Masashi Watanabe, Kyung Duk Moon, Melanie S Vacchio, Karen S Hathcock, Richard J HodesAbstract:Summary Antigen Specificity is critical in immune response and requires integration of Antigen-specific signals with Antigen-nonspecific signals such as those provided by cytokines. The mechanism integrating these pathways is incompletely understood. We report here that Antigen-specific proliferative responses of CD4 + T cells required downmodulation of tumor suppressor p53. In the absence of T cell receptor (TCR) signal, IL-2 induced sustained increase in p53 protein, which prevented proliferative responses despite strong signaling through the IL-2 receptor. In contrast, TCR signaling resulted in early termination of p53 protein expression by decreasing p53 mRNA as well as strong transcriptional induction of the p53-regulating protein Mdm2. Downmodulation of p53 in response to Antigen stimulation was in fact critical for Antigen-specific T cell proliferation, and preventing p53 degradation by inhibiting Mdm2 resulted in sustained p53 protein and prevented Antigen-specific T cell proliferation. It is thus termination of p53 by TCR signaling that allows proliferative responses, enforcing Antigen Specificity.
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Downmodulation of Tumor Suppressor p53 by T Cell Receptor Signaling Is Critical for Antigen-Specific CD4 + T Cell Responses
Immunity, 2014Co-Authors: Masashi Watanabe, Kyung Duk Moon, Melanie S Vacchio, Karen S Hathcock, Richard J HodesAbstract:Summary Antigen Specificity is critical in immune response and requires integration of Antigen-specific signals with Antigen-nonspecific signals such as those provided by cytokines. The mechanism integrating these pathways is incompletely understood. We report here that Antigen-specific proliferative responses of CD4 + T cells required downmodulation of tumor suppressor p53. In the absence of T cell receptor (TCR) signal, IL-2 induced sustained increase in p53 protein, which prevented proliferative responses despite strong signaling through the IL-2 receptor. In contrast, TCR signaling resulted in early termination of p53 protein expression by decreasing p53 mRNA as well as strong transcriptional induction of the p53-regulating protein Mdm2. Downmodulation of p53 in response to Antigen stimulation was in fact critical for Antigen-specific T cell proliferation, and preventing p53 degradation by inhibiting Mdm2 resulted in sustained p53 protein and prevented Antigen-specific T cell proliferation. It is thus termination of p53 by TCR signaling that allows proliferative responses, enforcing Antigen Specificity.
Nitin V. Kurkure - One of the best experts on this subject based on the ideXlab platform.
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Proteome-wide screening reveals immunodominance in the CD8 T cell response against classical swine fever virus with Antigen-Specificity dependent on MHC class I haplotype expression
2016Co-Authors: Giulia Franzoni, Nitin V. Kurkure, Sabine E. Essler, Miriam Pedrera, Helen E. Everett, Kikki B. Bodman-smith, Helen R. Crooke, Simon P. GrahamAbstract:Vaccination with live attenuated classical swine fever virus (CSFV) vaccines induces a rapid onset of protection which has been associated with virus-specific CD8 T cell IFN-c responses. In this study, we assessed the Specificity of this response, by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. Synthetic peptides were pooled to represent each of the 12 CSFV proteins and used to stimulate PBMC from four pigs rendered immune to CSFV by C-strain vaccination and subsequently challenged with the virulent Brescia strain. Significant IFN-c expression by CD8 T cells, assessed by flow cytometry, was induced by peptide pools representing the core, E2, NS2, NS3 and NS5A proteins. Dissection of these Antigenic peptide pools indicated that, in each instance, a single discrete Antigenic peptide or pair of overlapping peptides was responsible for the IFN-c induction. Screening and titration of Antigenic peptides or truncated derivatives identified the following Antigenic regions: core241–255 PESRKKLEKALLAWA and NS31902–1912 VEYSFIFLDEY, or minimal length Antigenic peptides: E2996–1003 YEPRDSYF, NS21223–1230 STVTGIFL and NS5A3070– 3078 RVDNALLKF. The epitopes are highly conserved across CSFV strains and variable sequence divergence was observed with related pestiviruses. Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-a in addition to IFN-c. Finally, the variability in the Antigen-Specificity of these immunodominant CD8 T cell responses was confirmed to be associated with expression o
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proteome wide screening reveals immunodominance in the cd8 t cell response against classical swine fever virus with Antigen Specificity dependent on mhc class i haplotype expression
PLOS ONE, 2013Co-Authors: Giulia Franzoni, Nitin V. Kurkure, Sabine E. Essler, Miriam Pedrera, Helen E. Everett, Helen R. Crooke, K Bodmansmith, Simon P. GrahamAbstract:Vaccination with live attenuated classical swine fever virus (CSFV) vaccines induces a rapid onset of protection which has been associated with virus-specific CD8 T cell IFN-γ responses. In this study, we assessed the Specificity of this response, by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. Synthetic peptides were pooled to represent each of the 12 CSFV proteins and used to stimulate PBMC from four pigs rendered immune to CSFV by C-strain vaccination and subsequently challenged with the virulent Brescia strain. Significant IFN-γ expression by CD8 T cells, assessed by flow cytometry, was induced by peptide pools representing the core, E2, NS2, NS3 and NS5A proteins. Dissection of these Antigenic peptide pools indicated that, in each instance, a single discrete Antigenic peptide or pair of overlapping peptides was responsible for the IFN-γ induction. Screening and titration of Antigenic peptides or truncated derivatives identified the following Antigenic regions: core241–255 PESRKKLEKALLAWA and NS31902–1912 VEYSFIFLDEY, or minimal length Antigenic peptides: E2996–1003 YEPRDSYF, NS21223–1230 STVTGIFL and NS5A3070–3078 RVDNALLKF. The epitopes are highly conserved across CSFV strains and variable sequence divergence was observed with related pestiviruses. Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-α in addition to IFN-γ. Finally, the variability in the Antigen-Specificity of these immunodominant CD8 T cell responses was confirmed to be associated with expression of distinct MHC class I haplotypes. Moreover, recognition of NS21223–1230 STVTGIFL and NS31902–1912 VEYSFIFLDEY by a larger group of C-strain vaccinated animals showed that these peptides could be restricted by additional haplotypes. Thus the Antigenic regions and epitopes identified represent attractive targets for evaluation of their vaccine potential against CSFV.