Immunodominant Epitopes

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Scheherazade Sadegh-nasseri - One of the best experts on this subject based on the ideXlab platform.

  • The love and hate relationship of HLA-DM/DO in the selection of Immunodominant Epitopes.
    Current opinion in immunology, 2020
    Co-Authors: Robin A Welsh, Scheherazade Sadegh-nasseri
    Abstract:

    Successful activation of CD4 T cells is centered around the ability of antigen presenting cells to successfully process, select Class II Immunodominant Epitopes from exogenous antigens and to present it to cognate T cells. To achieve this, newly synthesized MHC-II molecules are transferred to a specialized compartment which contain both exogenous antigens and the Class II processing machinery. Here in a process known as ‘editing,’ the Class II accessory molecule DM (HLA-DM human; murine H2-M) facilitates the loading and selection of exogenous peptides to MHC class II molecules thereby assuring proper selection of Immunodominant Epitopes. A second Class II accessory molecule, DO (HLA-DO human; murine H2-O), mainly present in B cells and thymic epithelium also contributes to the selection of Immunodominant Epitopes. Yet, despite a wealth of mechanistic insights into how DM functions, understanding the contributions of DO to epitope selection has proven to be highly challenging. In this review, we have attempted to discuss published in vitro and in vivo data during the past three years with insights into the biology of DO.

  • Selection of Immunodominant Epitopes during antigen processing is hierarchical.
    Molecular immunology, 2018
    Co-Authors: Scheherazade Sadegh-nasseri, Aeryon Kim
    Abstract:

    Abstract MHC II proteins present processed antigens to CD4 + T cells through a complex set of events and players that include chaperons and accessory molecules. Antigen processing machinery is optimized for the selection of the best fitting peptides, called ‘Immunodominant Epitopes’, in the MHC II groove to which, specific CD4 + T cells respond and differentiate into memory T cells. However, due to the complexity of antigen processing, understanding the parameters that lead to immunodominance has proved difficult. Moreover, immunodominance of Epitopes vary, depending on multiple factors that include; simultaneous processing of multiple proteins, involvement of multiple alleles of MHC II that can bind to the same antigen, or competition among several suitable Epitopes on a single protein antigen. The current dogma assumes that once an antigenic determinant is selected under a specific condition, it would emerge Immunodominant wherever it is placed. Here we will discuss some established parameters that contribute to immunodominance as well as some new findings, which demonstrate that slight changes to antigen structure can cause a complete shift in epitope selection during antigen processing and distort the natural Immunodominant epitope.

  • Distorted Immunodominance by Linker Sequences or other Epitopes from a Second Protein Antigen During Antigen-Processing
    Scientific Reports, 2017
    Co-Authors: Tatiana Boronina, Erika Darrah, Robert N Cole, Scheherazade Sadegh-nasseri
    Abstract:

    The immune system focuses on and responds to very few representative Immunodominant Epitopes from pathogenic insults. However, due to the complexity of the antigen processing, understanding the parameters that lead to immunodominance has proved difficult. In an attempt to uncover the determinants of immunodominance among several dominant Epitopes, we utilized a cell free antigen processing system and allowed the system to identify the hierarchies among potential determinants. We then tested the results in vivo; in mice and in human. We report here, that immunodominance of known sequences in a given protein can change if two or more proteins are being processed and presented simultaneously. Surprisingly, we find that new spacer/tag sequences commonly added to proteins for purification purposes can distort the capture of the physiological Immunodominant Epitopes. We warn against adding tags and spacers to candidate vaccines, or recommend cleaving it off before using for vaccination.

  • Divergent paths for the selection of Immunodominant Epitopes from distinct antigenic sources.
    Nature communications, 2014
    Co-Authors: Aeryon Kim, Tatiana Boronina, Robert N Cole, Isamu Z. Hartman, Brad Poore, Nianbin Song, M. Teresa Ciudad, Rachel R. Caspi, Dolores Jaraquemada, Scheherazade Sadegh-nasseri
    Abstract:

    Immunodominant Epitopes are few selected Epitopes from complex antigens that initiate T cell responses. Here, to provide further insights into this process, we use a reductionist cell-free antigen processing system composed of defined components. We use the system to characterize steps in antigen processing of pathogen-derived proteins or autoantigens and we find distinct paths for peptide processing and selection. Autoantigen-derived Immunodominant Epitopes are resistant to digestion by cathepsins, whereas pathogen-derived Epitopes are sensitive. Sensitivity to cathepsins enforces capture of pathogen-derived Epitopes by Major Histocompatibility Complex class II (MHC class II) prior to processing, and resistance to HLA-DM-mediated-dissociation preserves the longevity of those Epitopes. We show that immunodominance is established by higher relative abundance of the selected Epitopes, which survive cathepsin digestion either by binding to MHC class II and resisting DM-mediated-dissociation, or being chemically resistant to cathepsins degradation. Non-dominant Epitopes are sensitive to both DM and cathepsins and are destroyed.

Lun Zhang - One of the best experts on this subject based on the ideXlab platform.

  • the Immunodominant and neutralization linear Epitopes for sars cov 2
    Cell Reports, 2021
    Co-Authors: Xixiu Xie, Lei Zhao, Bin Wang, Jie Zhu, Tingrui Yang, Guangwen Yang, Jian Xue, Erhei Dai, Dongqun Liu, Lun Zhang
    Abstract:

    Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen Epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell Epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches and validate epitope immunogenicity by immunizing mice. Almost all 33 predicted Epitopes effectively induce antibody production, six of these are Immunodominant Epitopes in individuals, and 23 are conserved within SARS-CoV-2, SARS-CoV, and bat coronavirus RaTG13. We find that the Immunodominant Epitopes of individuals with domestic (China) SARS-CoV-2 are different from those of individuals with imported (Europe) SARS-CoV-2, which may be caused by mutations on the S (G614D) and N proteins. Importantly, we find several Epitopes on the S protein that elicit neutralizing antibodies against D614 and G614 SARS-CoV-2, which can contribute to vaccine design against coronaviruses.

  • the Immunodominant and neutralization linear Epitopes for sars cov 2
    bioRxiv, 2020
    Co-Authors: Xixiu Xie, Lei Zhao, Bin Wang, Jie Zhu, Tingrui Yang, Guangwen Yang, Jian Xue, Erhei Dai, Dongqun Liu, Lun Zhang
    Abstract:

    ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes a tremendous threat to global health. Although vaccines against the virus are under development, the antigen Epitopes on the virus and their immunogenicity are poorly understood. Here, we simulated the three-dimensional structures of SARS-CoV-2 proteins with high performance computer, predicted the B cell Epitopes on spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches, and then validated the epitope immunogenicity by immunizing mice. Almost all 33 predicted Epitopes effectively induced antibody production, six of which were Immunodominant Epitopes in patients identified via the binding of Epitopes with the sera from domestic and imported COVID-19 patients, and 23 were conserved within SARS-CoV-2, SARS-CoV and bat coronavirus RaTG13. We also found that the Immunodominant Epitopes of domestic SARS-CoV-2 were different from that of the imported, which may be caused by the mutations on S (G614D) and N proteins. Importantly, we validated that eight Epitopes on S protein elicited neutralizing antibodies that blocked the cell entry of both D614 and G614 pseudo-virus of SARS-CoV-2, three and nine Epitopes induced D614 or G614 neutralizing antibodies, respectively. Our present study shed light on the immunodominance, neutralization, and conserved Epitopes on SARS-CoV-2 which are potently used for the diagnosis, virus classification and the vaccine design tackling inefficiency, virus mutation and different species of coronaviruses.

Y. Mine - One of the best experts on this subject based on the ideXlab platform.

  • Immunomodulatory effects of egg white enzymatic hydrolysates containing Immunodominant Epitopes in a BALB/c mouse model of egg allergy.
    Journal of Agricultural and Food Chemistry, 2009
    Co-Authors: M. Yang, C.b. Yang, Francoise Nau, M. Pasco, L.r. Juneja, T. Okubo, Y. Mine
    Abstract:

    Egg has ben documented as a rich source for the supply of biologically active peptides. This study characterizes the immunomodulatory effects of an egg white enzymatic hydrolysate (EWH) using a BALB/c mouse model of egg allergy. Mice were orally sensitized to egg white and subsequently gavaged with EWH. ELISA results indicated significant reductions of both serum histamine and specific IgE titers in EWH-fed mice, accompanied by a repression of both IL-4 and IFN-gamma production in spleen cell cultures. Similarly, real-time RT-PCR analyses highlighted decreased mRNA expression of IFN-gamma and IL-12 (Th1-biased), as well as lower ratios of IL-4 and IL-13 mRNA (Th2-biased). On the other hand, increased intestinal expressions of TGF-beta and FOXp3 mRNA were determined in EWH-fed mice, suggesting induction of local regulatory mechanisms. The presence of Immunodominant Epitopes was proposed to be responsible for the immunomodulatory effects observed.

  • immunomodulatory effects of egg white enzymatic hydrolysates containing Immunodominant Epitopes in a balb c mouse model of egg allergy
    Journal of Agricultural and Food Chemistry, 2009
    Co-Authors: M. Yang, Francoise Nau, M. Pasco, L.r. Juneja, T. Okubo, Chengbo Yang, Y. Mine
    Abstract:

    Egg has ben documented as a rich source for the supply of biologically active peptides. This study characterizes the immunomodulatory effects of an egg white enzymatic hydrolysate (EWH) using a BALB/c mouse model of egg allergy. Mice were orally sensitized to egg white and subsequently gavaged with EWH. ELISA results indicated significant reductions of both serum histamine and specific IgE titers in EWH-fed mice, accompanied by a repression of both IL-4 and IFN-γ production in spleen cell cultures. Similarly, real-time RT-PCR analyses highlighted decreased mRNA expression of IFN-γ and IL-12 (Th1-biased), as well as lower ratios of IL-4 and IL-13 mRNA (Th2-biased). On the other hand, increased intestinal expressions of TGF-β and FOXp3 mRNA were determined in EWH-fed mice, suggesting induction of local regulatory mechanisms. The presence of Immunodominant Epitopes was proposed to be responsible for the immunomodulatory effects observed.

Davide Angeletti - One of the best experts on this subject based on the ideXlab platform.

  • outflanking immunodominance to target subdominant broadly neutralizing Epitopes
    Proceedings of the National Academy of Sciences of the United States of America, 2019
    Co-Authors: Jefferson J S Santos, William T Yewdell, Carolyn M Boudreau, Vamsee Aditya V Mallajosyula, Madeleine C Mankowski, Ivan Kosik, Davide Angeletti, Michael Chambers
    Abstract:

    A major obstacle to vaccination against antigenically variable viruses is skewing of antibody responses to variable Immunodominant Epitopes. For influenza virus hemagglutinin (HA), the immunodominance of the variable head impairs responses to the highly conserved stem. Here, we show that head immunodominance depends on the physical attachment of head to stem. Stem immunogenicity is enhanced by immunizing with stem-only constructs or by increasing local HA concentration in the draining lymph node. Surprisingly, coimmunization of full-length HA and stem alters stem-antibody class switching. Our findings delineate strategies for overcoming immunodominance, with important implications for human vaccination.

  • outflanking immunodominance to target subdominant broadly neutralizing Epitopes
    bioRxiv, 2018
    Co-Authors: Davide Angeletti, William T Yewdell, Carolyn M Boudreau, Vamsee Aditya V Mallajosyula, Michael Chambers, Adrian B Mcdermott, Ivan Kosik, Heather D Hickman, Madhu Prabhakaran, Galit Alter
    Abstract:

    A major obstacle to vaccination to antigenically variable viruses is skewing of antibody responses to Immunodominant Epitopes. For influenza virus hemagglutinin (HA), the immunodominance of the variable head impairs responses to the highly conserved stem. Here, we show that head immunodominance depends on the physical attachment of head to stem. Stem immunogenicity is enhanced by immunizing with stem only-constructs or by increasing local HA concentration in the draining lymph node. Surprisingly, co-immunization of HA and stem alters stem-antibody class switching. Our findings delineate strategies for overcoming immunodominance with important implications for human vaccination.

Xixiu Xie - One of the best experts on this subject based on the ideXlab platform.

  • the Immunodominant and neutralization linear Epitopes for sars cov 2
    Cell Reports, 2021
    Co-Authors: Xixiu Xie, Lei Zhao, Bin Wang, Jie Zhu, Tingrui Yang, Guangwen Yang, Jian Xue, Erhei Dai, Dongqun Liu, Lun Zhang
    Abstract:

    Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen Epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell Epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches and validate epitope immunogenicity by immunizing mice. Almost all 33 predicted Epitopes effectively induce antibody production, six of these are Immunodominant Epitopes in individuals, and 23 are conserved within SARS-CoV-2, SARS-CoV, and bat coronavirus RaTG13. We find that the Immunodominant Epitopes of individuals with domestic (China) SARS-CoV-2 are different from those of individuals with imported (Europe) SARS-CoV-2, which may be caused by mutations on the S (G614D) and N proteins. Importantly, we find several Epitopes on the S protein that elicit neutralizing antibodies against D614 and G614 SARS-CoV-2, which can contribute to vaccine design against coronaviruses.

  • the Immunodominant and neutralization linear Epitopes for sars cov 2
    bioRxiv, 2020
    Co-Authors: Xixiu Xie, Lei Zhao, Bin Wang, Jie Zhu, Tingrui Yang, Guangwen Yang, Jian Xue, Erhei Dai, Dongqun Liu, Lun Zhang
    Abstract:

    ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes a tremendous threat to global health. Although vaccines against the virus are under development, the antigen Epitopes on the virus and their immunogenicity are poorly understood. Here, we simulated the three-dimensional structures of SARS-CoV-2 proteins with high performance computer, predicted the B cell Epitopes on spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches, and then validated the epitope immunogenicity by immunizing mice. Almost all 33 predicted Epitopes effectively induced antibody production, six of which were Immunodominant Epitopes in patients identified via the binding of Epitopes with the sera from domestic and imported COVID-19 patients, and 23 were conserved within SARS-CoV-2, SARS-CoV and bat coronavirus RaTG13. We also found that the Immunodominant Epitopes of domestic SARS-CoV-2 were different from that of the imported, which may be caused by the mutations on S (G614D) and N proteins. Importantly, we validated that eight Epitopes on S protein elicited neutralizing antibodies that blocked the cell entry of both D614 and G614 pseudo-virus of SARS-CoV-2, three and nine Epitopes induced D614 or G614 neutralizing antibodies, respectively. Our present study shed light on the immunodominance, neutralization, and conserved Epitopes on SARS-CoV-2 which are potently used for the diagnosis, virus classification and the vaccine design tackling inefficiency, virus mutation and different species of coronaviruses.