LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 55

Search options

  1. Article: How a Proposed Hypothesis during My PhD Training Shaped My Career.

    Sadegh-Nasseri, Scheherazade

    Critical reviews in immunology

    2021  Volume 40, Issue 5, Page(s) 449–464

    Abstract: In this memoir-style essay, I have narrated the evolution of my scientific career, as deeply influenced by my PhD training and the mentorship of Professor Eli Sercarz. Starting in his lab, and continuing to my own laboratory, many of the questions we ... ...

    Abstract In this memoir-style essay, I have narrated the evolution of my scientific career, as deeply influenced by my PhD training and the mentorship of Professor Eli Sercarz. Starting in his lab, and continuing to my own laboratory, many of the questions we have pursued link in some way to Eli's ideas. In this essay, I have summarized the path that I followed after graduating from his lab and highlight findings along the way. I apologize to my colleagues whose work was not discussed here due to the nature of this review and space limitations.
    Language English
    Publishing date 2021-01-14
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 1353116-5
    ISSN 1040-8401
    ISSN 1040-8401
    DOI 10.1615/CritRevImmunol.2020035324
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Partnering for the major histocompatibility complex class II and antigenic determinant requires flexibility and chaperons.

    Sadegh-Nasseri, Scheherazade

    Current opinion in immunology

    2021  Volume 70, Page(s) 112–121

    Abstract: Cytotoxic, or helper T cells recognize antigen via T cell receptors (TCRs) that can see their target antigen as short sequences of peptides bound to the groove of proteins of major histocompatibility complex (MHC) class I, and class II respectively. For ... ...

    Abstract Cytotoxic, or helper T cells recognize antigen via T cell receptors (TCRs) that can see their target antigen as short sequences of peptides bound to the groove of proteins of major histocompatibility complex (MHC) class I, and class II respectively. For MHC class II epitope selection from exogenous pathogens or self-antigens, participation of several accessory proteins, molecular chaperons, processing enzymes within multiple vesicular compartments is necessary. A major contributing factor is the MHC class II structure itself that uniquely offers a dynamic and flexible groove essential for epitope selection. In this review, I have taken a historical perspective focusing on the flexibility of the MHC II molecules as the driving force in determinant selection and interactions with the accessory molecules in antigen processing, HLA-DM and HLA-DO.
    MeSH term(s) Animals ; Antigen Presentation/immunology ; Epitopes/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Molecular Chaperones/immunology
    Chemical Substances Epitopes ; Histocompatibility Antigens Class II ; Molecular Chaperones
    Language English
    Publishing date 2021-06-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2021.05.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Proper development of long-lived memory CD4 T cells requires HLA-DO function.

    Song, Nianbin / Welsh, Robin A / Sadegh-Nasseri, Scheherazade

    Frontiers in immunology

    2023  Volume 14, Page(s) 1277609

    Abstract: Introduction: HLA-DO (DO) is an accessory protein that binds DM for trafficking to MIIC and has peptide editing functions. DO is mainly expressed in thymic medulla and B cells. Using biochemical experiments, our lab has discovered that DO has ... ...

    Abstract Introduction: HLA-DO (DO) is an accessory protein that binds DM for trafficking to MIIC and has peptide editing functions. DO is mainly expressed in thymic medulla and B cells. Using biochemical experiments, our lab has discovered that DO has differential effects on editing peptides of different sequences: DO increases binding of DM-resistant peptides and reduces the binding of DM-sensitive peptides to the HLA-DR1 molecules. In a separate line of work, we have established that appropriate densities of antigen presentation by B cells during the contraction phase of an infection, induces quiescence in antigen experienced CD4 T cells, as they differentiate into memory T cells. This quiescence phenotype helps memory CD4 T cell survival and promotes effective memory responses to secondary Ag challenge.
    Methods: Based on our mechanistic understanding of DO function, it would be expected that if the immunodominant epitope of antigen is DM-resistant, presentation of decreased densities of pMHCII by B cells would lead to faulty development of memory CD4 T cells in the absence of DO. We explored the effects of DO on development of memory CD4 T cells and B cells utilizing two model antigens, H5N1-Flu Ag bearing DM-resistant, and OVA protein, which has a DM-sensitive immunodominant epitope and four mouse strains including two DO-deficient Tg mice. Using Tetramers and multiple antibodies against markers of memory CD4 T cells and B cells, we tracked memory development.
    Results: We found that immunized DR1
    Conclusion: These results demonstrate that in the absence of DO, the presentation of cognate foreign antigens in the DO-KO mice is altered and can impact the proper development of memory cells. These findings provide new insights on vaccination design leading to better immune memory responses.
    MeSH term(s) Animals ; Mice ; CD4-Positive T-Lymphocytes ; Immunodominant Epitopes ; Influenza A Virus, H5N1 Subtype/metabolism ; Memory T Cells ; Peptides
    Chemical Substances Immunodominant Epitopes ; Peptides ; H-2O antigen
    Language English
    Publishing date 2023-10-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1277609
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Editorial overview: Nature repeating itself: conformational flexibility determines MHC class I and class II epitope selection.

    Sadegh-Nasseri, Scheherazade / Springer, Sebastian

    Current opinion in immunology

    2021  Volume 70, Page(s) iii–iv

    MeSH term(s) Animals ; Histocompatibility Antigens Class I/chemistry ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class II/chemistry ; Histocompatibility Antigens Class II/immunology ; Humans ; Protein Conformation
    Chemical Substances Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II
    Language English
    Publishing date 2021-08-13
    Publishing country England
    Document type Editorial ; Introductory Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2021.07.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: H2-O deficiency promotes regulatory T cell differentiation and CD4 T cell hyperactivity.

    Welsh, Robin A / Song, Nianbin / Park, Chan-Su / Peske, J David / Sadegh-Nasseri, Scheherazade

    Frontiers in immunology

    2024  Volume 14, Page(s) 1304798

    Abstract: Regulatory T cells (Treg) are crucial immune modulators, yet the exact mechanism of thymic Treg development remains controversial. Here, we present the first direct evidence for H2-O, an MHC class II peptide editing molecular chaperon, on selection of ... ...

    Abstract Regulatory T cells (Treg) are crucial immune modulators, yet the exact mechanism of thymic Treg development remains controversial. Here, we present the first direct evidence for H2-O, an MHC class II peptide editing molecular chaperon, on selection of thymic Tregs. We identified that lack of H2-O in the thymic medulla promotes thymic Treg development and leads to an increased peripheral Treg frequency. Single-cell RNA-sequencing (scRNA-seq) analysis of splenic CD4 T cells revealed not only an enrichment of effector-like Tregs, but also activated CD4 T cells in the absence of H2-O. Our data support two concepts; a) lack of H2-O expression in the thymic medulla creates an environment permissive to Treg development and, b) that loss of H2-O drives increased basal auto-stimulation of CD4 T cells. These findings can help in better understanding of predispositions to autoimmunity and design of therapeutics for treatment of autoimmune diseases.
    MeSH term(s) Humans ; CD4-Positive T-Lymphocytes ; Lymphocyte Activation/genetics ; T-Lymphocytes, Regulatory ; Histocompatibility Antigens Class II ; Autoimmune Diseases ; Cell Differentiation
    Chemical Substances Histocompatibility Antigens Class II
    Language English
    Publishing date 2024-01-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1304798
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article: Discovering how DO regulates lymphocyte function

    Sadegh-Nasseri, Scheherazade / Song, Nianbin / Welsh, Robin

    Molecular immunology. 2022 Oct., v. 150

    2022  

    Abstract: HLA-DO or H-2O (DO) in mice is a non-classical, non-polymorphic MHC II molecule primarily expressed in the thymic medulla and B cells. While the common belief is that DO inhibits the activity of DM, controversial data opposes that point of view. Applying ...

    Abstract HLA-DO or H-2O (DO) in mice is a non-classical, non-polymorphic MHC II molecule primarily expressed in the thymic medulla and B cells. While the common belief is that DO inhibits the activity of DM, controversial data opposes that point of view. Applying physicochemical studies to purified DO, DM, and HLA-DR1, we have demonstrated that DO interacts directly with HLA-DR1 molecules in a peptide-receptive-conformation, augmenting binding of ‘DM-resistant’ peptides, while inhibiting binding of ‘DM-sensitive’ peptides to HLA-DR1. Indeed, we have observed that DO-WT B cells express higher densities of pMHC from naturally processed protein antigens in vivo. Accordingly, DO-KO mice are more susceptible to development of EAE due to presence of larger numbers MOG/IAb-specific CD4 T cells in periphery, likely due to a less effective thymic deletion. Since DO is also expressed in B cells, and B cell antigen presentation is a critical step in differentiation of CD4 memory T cells, we tested the contributions of DO to the development of CD4 memory T cells. To do so, we used DR1+/DO-KO mice, and examined CD4 memory development to DR1 restricted flu specific T cells three months post flu vaccine immunization. We found that consistent with our hypothesis, the DR1+/DO-KO mice had fewer flu specific CD4 memory T cells than DR1+/DO-WT mice. By in vitro and in vivo recall experiments, we also found that the secondary immunological responses in DR1+/DO-KO mice were compromised. In addition, we recovered fewer memory B cells from immunized DR1+/DO-KO mice. These results demonstrate that in the absence of DO, the presentation of cognate foreign antigens in the DO-KO mice is altered and can potentially hamper the proper development of memory cells after the resolution of the infection. These findings support the idea that the expression of DO might ensure the proper development of memory cells.
    Keywords B-lymphocytes ; CD4-positive T-lymphocytes ; antigen presentation ; immunization ; influenza ; influenza vaccines ; memory ; peptides
    Language English
    Dates of publication 2022-10
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 424427-8
    ISSN 1872-9142 ; 0161-5890
    ISSN (online) 1872-9142
    ISSN 0161-5890
    DOI 10.1016/j.molimm.2022.05.109
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  7. Article: H2-O deficiency promotes regulatory T cell differentiation and CD4 T cell hyperactivity.

    Welsh, Robin A / Song, Nianbin / Park, Chan-Su / Peske, J David / Sadegh-Nasseri, Scheherazade

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Regulatory T cells (Treg) are crucial immune modulators, yet the exact mechanism of thymic Treg development remains controversial. Here, we present the first direct evidence for H2-O, an MHC class II peptide editing molecular chaperon, on selection of ... ...

    Abstract Regulatory T cells (Treg) are crucial immune modulators, yet the exact mechanism of thymic Treg development remains controversial. Here, we present the first direct evidence for H2-O, an MHC class II peptide editing molecular chaperon, on selection of thymic Tregs. We provide evidence that lack of H2-O in the thymic medulla promotes thymic Treg development and leads to an increased peripheral Treg frequency. Single-cell RNA-sequencing (scRNA-seq) analysis of splenic CD4 T cells revealed not only of an enrichment of effector-like Tregs but also of activated CD4 T cells in the absence of H2-O. Our data support two concepts; a) lack of H2-O expression in the thymic medulla creates an environment permissive to Treg development and, b) that loss of H2-O drives increased basal auto-stimulation of CD4 T cells. These findings can help in better understanding of predispositions to autoimmunity and design of therapeutics for treatment of autoimmune diseases.
    Language English
    Publishing date 2023-09-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.14.553240
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: How Does B Cell Antigen Presentation Affect Memory CD4 T Cell Differentiation and Longevity?

    Welsh, Robin A / Song, Nianbin / Sadegh-Nasseri, Scheherazade

    Frontiers in immunology

    2021  Volume 12, Page(s) 677036

    Abstract: Dendritic cells are the antigen presenting cells that process antigens effectively and prime the immune system, a characteristic that have gained them the spotlights in recent years. B cell antigen presentation, although less prominent, deserves equal ... ...

    Abstract Dendritic cells are the antigen presenting cells that process antigens effectively and prime the immune system, a characteristic that have gained them the spotlights in recent years. B cell antigen presentation, although less prominent, deserves equal attention. B cells select antigen experienced CD4 T cells to become memory and initiate an orchestrated genetic program that maintains memory CD4 T cells for life of the individual. Over years of research, we have demonstrated that low levels of antigens captured by B cells during the resolution of an infection render antigen experienced CD4 T cells into a quiescent/resting state. Our studies suggest that in the absence of antigen, the resting state associated with low-energy utilization and proliferation can help memory CD4 T cells to survive nearly throughout the lifetime of mice. In this review we would discuss the primary findings from our lab as well as others that highlight our understanding of B cell antigen presentation and the contributions of the MHC Class II accessory molecules to this outcome. We propose that the quiescence induced by the low levels of antigen presentation might be a mechanism necessary to regulate long-term survival of CD4 memory T cells and to prevent cross-reactivity to autoantigens, hence autoimmunity.
    MeSH term(s) Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; Antigens/immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cell Differentiation/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunologic Memory ; Longevity/immunology ; Lymphocyte Activation/immunology ; Mice
    Chemical Substances Antigens ; Histocompatibility Antigens Class II
    Language English
    Publishing date 2021-06-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.677036
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Commensal bacteria maintain a Qa-1

    Guan, Jian / Peske, J David / Manoharan Valerio, Michael / Park, Chansu / Robey, Ellen A / Sadegh-Nasseri, Scheherazade

    eLife

    2023  Volume 12

    Abstract: Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of ... ...

    Abstract Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8
    MeSH term(s) Animals ; Mice ; CD8-Positive T-Lymphocytes ; Epithelium ; Bacteria ; Cytokines ; Intestinal Mucosa
    Chemical Substances Cytokines
    Language English
    Publishing date 2023-12-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.90466
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article: Commensal Bacteria Maintain a Qa-1

    Guan, Jian / Peske, J David / Valerio, Michael Manoharan / Park, Chansu / Robey, Ellen A / Sadegh-Nasseri, Scheherazade

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of ... ...

    Abstract Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8
    Language English
    Publishing date 2023-10-11
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.01.530600
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top