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  1. Article ; Online: Lipid rafts, pseudotyping, and virus-like particles: relevance of a novel, configurable, and modular antigen-presenting platform.

    Kueng, Hans J / Schmetterer, Klaus G / Pickl, Winfried F

    International archives of allergy and immunology

    2011  Volume 154, Issue 2, Page(s) 89–110

    Abstract: Antigen presentation by professional antigen-presenting cells (APC) is the first step towards the initiation of an adaptive immune response carried out by naïve T lymphocytes. For this purpose, antigens are presented in the form of peptide/major ... ...

    Abstract Antigen presentation by professional antigen-presenting cells (APC) is the first step towards the initiation of an adaptive immune response carried out by naïve T lymphocytes. For this purpose, antigens are presented in the form of peptide/major histocompatibility complexes (pMHC) on APC to the antigen receptor of T cells. For sustained T cell activation to occur, numerous additional molecules specifically expressed on the surface of APC have to synergize with pMHC to stimulate a given T lymphocyte. Moreover, soluble factors such as cytokines critically contribute to the specific milieu during T cell activation. APC 'talk' to T cells only when they engage in intimate physical interaction. The cell biological correlate of this APC-T cell interaction is commonly referred to as the formation of an immunological synapse. In this review we aim to provide an overview of a novel cell-free antigen-presenting platform, i.e. virus-like particles (VLP) decorated with immune receptors of choice, which was devised to overcome the molecular and cell biological complexity of the APC side of the immunological synapse. In the past we have demonstrated that immune receptor-decorated VLP are able to activate, modulate, or abrogate antigen-specific T lymphocyte responses. Thus, antigen-specific VLP represent a valuable tool which might help to explore and understand the function of antigen-specific T lymphocytes in more detail and might thus open new avenues for the modulation of pathologic T lymphocyte responses, e.g. for the treatment of allergic diseases.
    MeSH term(s) Antigen Presentation/immunology ; Humans ; Immunological Synapses/immunology ; Lymphocyte Activation/immunology ; Membrane Microdomains/immunology ; T-Lymphocytes/immunology ; Virion/immunology
    Language English
    Publishing date 2011
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1108932-5
    ISSN 1423-0097 ; 1018-2438
    ISSN (online) 1423-0097
    ISSN 1018-2438
    DOI 10.1159/000320224
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  2. Article: Behandlung des fortgeschrittenen Prostatakarzinoms – eine interdisziplinäre Empfehlung.

    Omlin, Aurelius / Spahn, Martin / Beyer, Jörg / Eberli, Daniel / Gillessen, Silke / Jochum, Wolfram / Kueng, Marc / Nitzsche, Egbert / Rentsch, Cyrill A / Roggero, Enrico / Schmid, Hans-Peter / Stenner, Frank / Templeton, Arnoud J / Wild, Damian / Wyler, Stephen / Zwahlen, Daniel / Cathomas, Richard

    Praxis

    2018  Volume 107, Issue 19, Page(s) 1043–1051

    Title translation Treatment of Advanced Prostate Carcinoma - an Interdisciplinary Recommendation.
    MeSH term(s) Androgen Antagonists/therapeutic use ; Biomarkers, Tumor/genetics ; Humans ; Interdisciplinary Communication ; Intersectoral Collaboration ; Male ; Neoplasm Metastasis ; Neoplasm Staging ; Orchiectomy ; Prognosis ; Prostatectomy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/therapy ; Prostatic Neoplasms, Castration-Resistant/pathology ; Prostatic Neoplasms, Castration-Resistant/therapy ; Radiotherapy, Adjuvant ; Salvage Therapy
    Chemical Substances Androgen Antagonists ; Biomarkers, Tumor
    Language German
    Publishing date 2018-09-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 209026-0
    ISSN 1661-8165 ; 1661-8157 ; 0369-8394
    ISSN (online) 1661-8165
    ISSN 1661-8157 ; 0369-8394
    DOI 10.1024/1661-8157/a003054
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  3. Article: Lipid Rafts, Pseudotyping, and Virus-Like Particles: Relevance of a Novel, Configurable, and Modular Antigen-Presenting Platform

    Kueng, Hans J. / Schmetterer, Klaus G. / Pickl, Winfried F.

    International Archives of Allergy and Immunology

    2010  Volume 154, Issue 2, Page(s) 89–110

    Abstract: Antigen presentation by professional antigen-presenting cells (APC) is the first step towards the initiation of an adaptive immune response carried out by naïve T lymphocytes. For this purpose, antigens are presented in the form of peptide/major ... ...

    Institution Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, and Christian Doppler Laboratory for Immunomodulation, Vienna, Austria
    Abstract Antigen presentation by professional antigen-presenting cells (APC) is the first step towards the initiation of an adaptive immune response carried out by naïve T lymphocytes. For this purpose, antigens are presented in the form of peptide/major histocompatibility complexes (pMHC) on APC to the antigen receptor of T cells. For sustained T cell activation to occur, numerous additional molecules specifically expressed on the surface of APC have to synergize with pMHC to stimulate a given T lymphocyte. Moreover, soluble factors such as cytokines critically contribute to the specific milieu during T cell activation. APC ‘talk’ to T cells only when they engage in intimate physical interaction. The cell biological correlate of this APC-T cell interaction is commonly referred to as the formation of an immunological synapse. In this review we aim to provide an overview of a novel cell-free antigen-presenting platform, i.e. virus-like particles (VLP) decorated with immune receptors of choice, which was devised to overcome the molecular and cell biological complexity of the APC side of the immunological synapse. In the past we have demonstrated that immune receptor-decorated VLP are able to activate, modulate, or abrogate antigen-specific T lymphocyte responses. Thus, antigen-specific VLP represent a valuable tool which might help to explore and understand the function of antigen-specific T lymphocytes in more detail and might thus open new avenues for the modulation of pathologic T lymphocyte responses, e.g. for the treatment of allergic diseases.
    Keywords Antigen presentation ; Virus-like particles ; Lipid rafts ; Pseudotyping
    Language English
    Publishing date 2010-08-24
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Review
    ZDB-ID 1108932-5
    ISSN 1423-0097 ; 1018-2438
    ISSN (online) 1423-0097
    ISSN 1018-2438
    DOI 10.1159/000320224
    Database Karger publisher's database

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  4. Article ; Online: Bet v 1-specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1-specific T-cell effector function in an activation-dependent manner.

    Schmetterer, Klaus G / Haiderer, Daniela / Leb-Reichl, Victoria M / Neunkirchner, Alina / Jahn-Schmid, Beatrice / Küng, Hans J / Schuch, Karina / Steinberger, Peter / Bohle, Barbara / Pickl, Winfried F

    The Journal of allergy and clinical immunology

    2011  Volume 127, Issue 1, Page(s) 238–45, 245.e1–3

    Abstract: Background: Regulatory T (Treg) cells establish and maintain tolerance to self-antigens and many foreign antigens, such as allergens, by suppressing effector T-cell proliferation and function. We have previously shown that human T-cell receptor (TCR) αβ- ...

    Abstract Background: Regulatory T (Treg) cells establish and maintain tolerance to self-antigens and many foreign antigens, such as allergens, by suppressing effector T-cell proliferation and function. We have previously shown that human T-cell receptor (TCR) αβ-chains specific for allergen-derived epitopes confer allergen specificity on peripheral blood T cells of individuals with and without allergy.
    Objective: To study the feasibility of generating allergen-specific human Treg cells by retroviral transduction of a transcription unit encoding forkhead box protein 3 (FOXP3) and allergen-specific TCR αβ-chains.
    Methods: cDNAs encoding the α and β-chains of a Bet v 1(142-153)-specific TCR (TCR alpha variable region 6/TCR beta variable region 20) and human FOXP3 were linked via picornaviral 2A sequences and expressed as single translational unit from an internal ribosomal entry site-green fluorescence protein-containing retroviral vector. Retrovirally transduced peripheral blood T cells were tested for expression of transgenes, Treg phenotype, and regulatory capacity toward allergen-specific effector T cells.
    Results: Transduced T cells displayed a Treg phenotype with clear-cut upregulation of CD25, CD39, and cytotoxic T-lymphocyte antigen 4. The transduced cells were hyporesponsive in cytokine production and secretion and, like naturally occurring Treg cells, did not proliferate after antigen-specific or antigen-mimetic stimulation. However, proliferation was inducible upon exposure to exogenous IL-2. In coculture experiments, TRAV6(+)TRBV20(+)FOXP3(+) transgenic T cells, unlike FOXP3(+) single transgenic T cells or naturally occurring Treg cells, highly significantly suppressed T cell cytokine production and proliferation of corresponding allergen-specific effector T cells in an allergen-specific, dose-dependent manner.
    Conclusion: We demonstrate a transgenic approach to engineer human allergen-specific Treg cells that exert their regulatory function in an activation-dependent manner. Customized Treg cells might become useful for tolerance induction therapies in individuals with allergic and other immune-mediated diseases.
    MeSH term(s) Allergens/genetics ; Allergens/immunology ; Antigens, Plant/genetics ; Antigens, Plant/immunology ; Betula ; Cell Separation ; Flow Cytometry ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/immunology ; Genetic Engineering/methods ; Genetic Vectors ; HEK293 Cells ; Humans ; Lymphocyte Activation/immunology ; Pollen ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Retroviridae ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Transduction, Genetic ; Transfection ; Transgenes
    Chemical Substances Allergens ; Antigens, Plant ; FOXP3 protein, human ; Forkhead Transcription Factors ; Receptors, Antigen, T-Cell, alpha-beta
    Language English
    Publishing date 2011-01-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2010.10.023
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  5. Article ; Online: Human TCR transgenic Bet v 1-specific Th1 cells suppress the effector function of Bet v 1-specific Th2 cells.

    Neunkirchner, Alina / Leb-Reichl, Victoria M / Schmetterer, Klaus G / Mutschlechner, Sonja / Kueng, Hans J / Haiderer, Daniela / Schuch, Karina / Wallner, Michael / Jahn-Schmid, Beatrice / Bohle, Barbara / Pickl, Winfried F

    Journal of immunology (Baltimore, Md. : 1950)

    2011  Volume 187, Issue 8, Page(s) 4077–4087

    Abstract: Pollinosis to birch pollen is a common type I allergy in the Northern Hemisphere. Moreover, birch pollen-allergic individuals sensitized to the major birch pollen allergen Bet v 1 frequently develop allergic reactions to stone fruits, hazelnuts, and ... ...

    Abstract Pollinosis to birch pollen is a common type I allergy in the Northern Hemisphere. Moreover, birch pollen-allergic individuals sensitized to the major birch pollen allergen Bet v 1 frequently develop allergic reactions to stone fruits, hazelnuts, and certain vegetables due to immunological cross-reactivity. The major T cell epitope Bet v 1(142-153) plays an important role in cross-reactivity between the respiratory allergen Bet v 1 and its homologous food allergens. In this study, we cloned and functionally analyzed a human αβ TCR specific for the immunodominant epitope Bet v 1(142-153). cDNAs encoding TCR α- and β-chains were amplified from a Bet v 1(142-153)-specific T cell clone, introduced into Jurkat T cells and peripheral blood T lymphocytes of allergic and nonallergic individuals, and evaluated functionally. The resulting TCR transgenic (TCRtg) T cells responded in an allergen-specific and costimulation-dependent manner to APCs either pulsed with Bet v 1(142-153) peptide or coexpressing invariant chain::Bet v 1(142-153) fusion proteins. TCRtg T cells responded to Bet v 1-related food and tree pollen allergens that were processed and presented by monocyte-derived dendritic cells. Bet v 1(142-153)-presenting but not Bet v 1(4-15)-presenting artificial APCs coexpressing membrane-bound IL-12 polarized allergen-specific TCRtg T cells toward a Th1 phenotype, producing high levels of IFN-γ. Coculture of such Th1-polarized T cells with allergen-specific Th2-differentiated T cells significantly suppressed Th2 effector cytokine production. These data suggest that human allergen-specific TCR can transfer the fine specificity of the original T cell clone to heterologous T cells, which in turn can be instructed to modulate the effector function of the disease initiating/perpetuating allergen-specific Th2-differentiated T cells.
    MeSH term(s) Amino Acid Sequence ; Antigens, Plant/immunology ; Base Sequence ; Cell Separation ; Cross Reactions/immunology ; Flow Cytometry ; Fluorescent Antibody Technique ; Food Hypersensitivity/immunology ; HEK293 Cells ; Humans ; Immunodominant Epitopes/immunology ; Jurkat Cells ; Lymphocyte Activation/immunology ; Molecular Sequence Data ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Reverse Transcriptase Polymerase Chain Reaction ; Rhinitis, Allergic, Seasonal/immunology ; Th1 Cells/immunology ; Th2 Cells/immunology ; Transduction, Genetic ; Transgenes
    Chemical Substances Antigens, Plant ; Immunodominant Epitopes ; Receptors, Antigen, T-Cell, alpha-beta ; Bet v 1 allergen, Betula (126161-14-6)
    Language English
    Publishing date 2011-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1003220
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  6. Article ; Online: Fluorosomes: a convenient new reagent to detect and block multivalent and complex receptor-ligand interactions.

    Kueng, Hans J / Manta, Calin / Haiderer, Daniela / Leb, Victoria M / Schmetterer, Klaus G / Neunkirchner, Alina / Byrne, Ruth A / Scheinecker, Clemens / Steinberger, Peter / Seed, Brian / Pickl, Winfried F

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2010  Volume 24, Issue 5, Page(s) 1572–1582

    Abstract: We describe for the first time fluorescent virus-like particles decorated with biologically active mono- and multisubunit immune receptors of choice and the basic application of such fluorosomes (FSs) to visualize and target immune receptor-ligand ... ...

    Abstract We describe for the first time fluorescent virus-like particles decorated with biologically active mono- and multisubunit immune receptors of choice and the basic application of such fluorosomes (FSs) to visualize and target immune receptor-ligand interactions. For that purpose, human embryonic kidney (HEK)-293 cells were stably transfected with Moloney murine leukemia virus (MoMLV) matrix protein (MA) GFP fusion constructs. To produce FSs, interleukins (ILs), IL-receptors (IL-Rs), and costimulatory molecules were fused to the glycosyl phosphatidyl inositol anchor acceptor sequence of CD16b and coexpressed along with MoMLV group-specific antigen-polymerase (gag-pol) in MA::GFP(+) HEK-293 cells. We show that IL-2 decorated but not control-decorated FSs specifically identify normal and malignant IL-2 receptor-positive (IL-2R(+)) lymphocytes by flow cytometry. In addition to cytokines and costimulatory molecules, FSs were also successfully decorated with the heterotrimeric IL-2Rs, allowing identification of IL-2(+) target cells. Specificity of binding was proven by complete inhibition with nonlabeled, soluble ligands. Moreover, IL-2R FSs efficiently neutralized soluble IL-2 and thus induced unresponsiveness of T cells receiving full activation stimuli via T-cell antigen receptor and CD28. FSs are technically simple, multivalent tools for assessing and blocking mono- and multisubunit immune receptor-ligand interactions with natural constituents in a plasma membrane context.
    MeSH term(s) Cell Line, Transformed ; Fluorescence ; Fluorescent Dyes/chemistry ; GPI-Linked Proteins ; Green Fluorescent Proteins/chemistry ; Green Fluorescent Proteins/genetics ; Humans ; Interleukin-2/analysis ; Interleukin-2/immunology ; Ligands ; Lymphoma, B-Cell/diagnosis ; Lymphoma, B-Cell/immunology ; Microscopy, Confocal ; Moloney murine leukemia virus ; Receptors, IgG ; Receptors, Interleukin-2/analysis ; Receptors, Interleukin-2/immunology ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; T-Lymphocytes/immunology ; Virion/chemistry ; Virion/genetics
    Chemical Substances FCGR3B protein, human ; Fluorescent Dyes ; GPI-Linked Proteins ; Interleukin-2 ; Ligands ; Receptors, IgG ; Receptors, Interleukin-2 ; Recombinant Proteins ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2010-01-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.09-137281
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  7. Article: Fluorosomes: a convenient new reagent to detect and block multivalent and complex receptor-ligand interactions

    Kueng, Hans J / Manta, Calin / Haiderer, Daniela / Leb, Victoria M / Schmetterer, Klaus G / Neunkirchner, Alina / Byrne, Ruth A / Scheinecker, Clemens / Steinberger, Peter / Seed, Brian / Pickl, Winfried F

    FASEB journal. 2010 May, v. 24, no. 5

    2010  

    Abstract: ... H. J., Manta, C., Haiderer, D., Leb, V. M., Schmetterer, K. G., Neunkirchner, A., Byrne, R ... multisubunit immune receptor-ligand interactions with natural constituents in a plasma membrane context.--Kueng ...

    Abstract We describe for the first time fluorescent virus-like particles decorated with biologically active mono- and multisubunit immune receptors of choice and the basic application of such fluorosomes (FSs) to visualize and target immune receptor-ligand interactions. For that purpose, human embryonic kidney (HEK)-293 cells were stably transfected with Moloney murine leukemia virus (MoMLV) matrix protein (MA) GFP fusion constructs. To produce FSs, interleukins (ILs), IL-receptors (IL-Rs), and costimulatory molecules were fused to the glycosyl phosphatidyl inositol anchor acceptor sequence of CD16b and coexpressed along with MoMLV group-specific antigen-polymerase (gag-pol) in MA::GFP⁺ HEK-293 cells. We show that IL-2 decorated but not control-decorated FSs specifically identify normal and malignant IL-2 receptor-positive (IL-2R⁺) lymphocytes by flow cytometry. In addition to cytokines and costimulatory molecules, FSs were also successfully decorated with the heterotrimeric IL-2Rs, allowing identification of IL-2⁺ target cells. Specificity of binding was proven by complete inhibition with nonlabeled, soluble ligands. Moreover, IL-2R FSs efficiently neutralized soluble IL-2 and thus induced unresponsiveness of T cells receiving full activation stimuli via T-cell antigen receptor and CD28. FSs are technically simple, multivalent tools for assessing and blocking mono- and multisubunit immune receptor-ligand interactions with natural constituents in a plasma membrane context.--Kueng, H. J., Manta, C., Haiderer, D., Leb, V. M., Schmetterer, K. G., Neunkirchner, A., Byrne, R. A., Scheinecker, C., Steinberger, P., Seed, B., Pickl, W. F. Fluorosomes: a convenient new reagent to detect and block multivalent and complex receptor-ligand interactions.
    Language English
    Dates of publication 2010-05
    Size p. 1572-1582.
    Publishing place The Federation of American Societies for Experimental Biology
    Document type Article
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
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  8. Article: Bet v 1–specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1–specific T-cell effector function in an activation-dependent manner

    Schmetterer, Klaus G / Haiderer, Daniela / Leb-Reichl, Victoria M / Neunkirchner, Alina / Jahn-Schmid, Beatrice / Küng, Hans J / Schuch, Karina / Steinberger, Peter / Bohle, Barbara / Pickl, Winfried F

    The Journal of Allergy and Clinical Immunology. 2011 Jan., v. 127, no. 1

    2011  

    Abstract: BACKGROUND: Regulatory T (Treg) cells establish and maintain tolerance to self-antigens and many foreign antigens, such as allergens, by suppressing effector T-cell proliferation and function. We have previously shown that human T-cell receptor (TCR) αβ- ... ...

    Abstract BACKGROUND: Regulatory T (Treg) cells establish and maintain tolerance to self-antigens and many foreign antigens, such as allergens, by suppressing effector T-cell proliferation and function. We have previously shown that human T-cell receptor (TCR) αβ-chains specific for allergen-derived epitopes confer allergen specificity on peripheral blood T cells of individuals with and without allergy. OBJECTIVE: To study the feasibility of generating allergen-specific human Treg cells by retroviral transduction of a transcription unit encoding forkhead box protein 3 (FOXP3) and allergen-specific TCR αβ-chains. METHODS: cDNAs encoding the α and β−chains of a Bet v 1₁₄₂₋₁₅₃−specific TCR (TCR alpha variable region 6/TCR beta variable region 20) and human FOXP3 were linked via picornaviral 2A sequences and expressed as single translational unit from an internal ribosomal entry site—green fluorescence protein−containing retroviral vector. Retrovirally transduced peripheral blood T cells were tested for expression of transgenes, Treg phenotype, and regulatory capacity toward allergen-specific effector T cells. RESULTS: Transduced T cells displayed a Treg phenotype with clear-cut upregulation of CD25, CD39, and cytotoxic T-lymphocyte antigen 4. The transduced cells were hyporesponsive in cytokine production and secretion and, like naturally occurring Treg cells, did not proliferate after antigen-specific or antigen-mimetic stimulation. However, proliferation was inducible upon exposure to exogenous IL-2. In coculture experiments, TRAV6⁺TRBV20⁺FOXP3⁺ transgenic T cells, unlike FOXP3⁺ single transgenic T cells or naturally occurring Treg cells, highly significantly suppressed T cell cytokine production and proliferation of corresponding allergen-specific effector T cells in an allergen-specific, dose-dependent manner. CONCLUSION: We demonstrate a transgenic approach to engineer human allergen-specific Treg cells that exert their regulatory function in an activation-dependent manner. Customized Treg cells might become useful for tolerance induction therapies in individuals with allergic and other immune-mediated diseases.
    Keywords T-lymphocytes ; allergens ; coculture ; complementary DNA ; cytotoxicity ; dose response ; epitopes ; fluorescence ; gene expression regulation ; genetically modified organisms ; humans ; hypersensitivity ; interleukin-2 ; phenotype ; retroviral vectors ; secretion ; transgenes ; translation (genetics)
    Language English
    Dates of publication 2011-01
    Size p. 238-245.e3.
    Publishing place Mosby, Inc.
    Document type Article
    ZDB-ID 121011-7
    ISSN 1085-8725 ; 1097-6825 ; 0091-6749
    ISSN (online) 1085-8725 ; 1097-6825
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2010.10.023
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  9. Article ; Online: Modulation of allergen-specific T-lymphocyte function by virus-like particles decorated with HLA class II molecules.

    Leb, Victoria M / Jahn-Schmid, Beatrice / Kueng, Hans J / Schmetterer, Klaus G / Haiderer, Daniela / Neunkirchner, Alina / Fischer, Gottfried F / Hartl, Arnulf / Thalhamer, Josef / Steinberger, Peter / Bohle, Barbara / Seed, Brian / Pickl, Winfried F

    The Journal of allergy and clinical immunology

    2009  Volume 124, Issue 1, Page(s) 121–128

    Abstract: Background: T(H)2 lymphocytes play an important role in the induction and maintenance phase of type I allergy. Modulation of the responses of T(H)2 lymphocytes by novel forms of antigen-presenting platforms may help shape the immune response to allergen ...

    Abstract Background: T(H)2 lymphocytes play an important role in the induction and maintenance phase of type I allergy. Modulation of the responses of T(H)2 lymphocytes by novel forms of antigen-presenting platforms may help shape the immune response to allergen and palliate allergic diseases.
    Objective: To present HLA class II/allergen-peptide complexes on virus-like particles (VLPs) and to evaluate their potential to modulate allergen-specific T-cell responses.
    Methods: Virus-like particles that express the immunodominant T-cell epitope Art v 1(25-34) of the major mugwort pollen allergen in the context of HLA-DR1 and costimulatory molecules were produced by transfection of 293 cells. The effect of VLPs on IL-2 promoter activity, proliferation, and cytokine production of allergen-specific T cells derived from donors with and without mugwort pollen allergy was determined.
    Results: Flow-cytometric analyses showed that HLA class II molecules, invariant chain::Art v 1 fusion proteins, and costimulatory molecules were expressed on 293 cells. Biochemical analyses confirmed that these molecules were efficiently targeted to VLPs. The engineered VLPs activated Art v 1-specific T cells in a costimulation-dependent manner. VLPs lacking costimulators induced T-cell unresponsiveness, which was overcome by addition of exogenous IL-2. Costimulation could be provided by CD80, CD86, or CD58 and induced distinct cytokine profiles in allergen-specific T cells. Unlike the other costimulatory molecules, CD58 induced IL-10/IFN-gamma-secreting T cells.
    Conclusion: Virus-like particles represent a novel, modular, acellular antigen-presenting system able to modulate the responses of allergen-specific T cells in a costimulator-dependent fashion. Allergen-specific VLPs show promise as tools for specific immunotherapy of allergic diseases.
    MeSH term(s) Cell Line ; Cloning, Molecular ; Cytokines/immunology ; Genetic Vectors/genetics ; HLA-A Antigens/genetics ; HLA-A Antigens/metabolism ; HLA-A Antigens/pharmacology ; HLA-DR Antigens/genetics ; HLA-DR Antigens/metabolism ; HLA-DR Antigens/pharmacology ; HLA-DRB1 Chains ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunization/methods ; Jurkat Cells ; Kidney/cytology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Virion/genetics
    Chemical Substances Cytokines ; HLA-A Antigens ; HLA-DR Antigens ; HLA-DRB1 Chains ; HLA-DRB1*01:01 antigen ; Histocompatibility Antigens Class II
    Language English
    Publishing date 2009-06-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2009.04.008
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  10. Article ; Online: Molecular and functional analysis of the antigen receptor of Art v 1-specific helper T lymphocytes.

    Leb, Victoria M / Jahn-Schmid, Beatrice / Schmetterer, Klaus G / Kueng, Hans J / Haiderer, Daniela / Neunkirchner, Alina / Fischer, Gottfried F / Nissler, Karl / Hartl, Arnulf / Thalhamer, Josef / Bohle, Barbara / Seed, Brian / Pickl, Winfried F

    The Journal of allergy and clinical immunology

    2007  Volume 121, Issue 1, Page(s) 64–71

    Abstract: Background: Ninety-five percent of patients with mugwort allergy are sensitized to Art v 1, the sole major allergen in mugwort (Artemisia vulgaris) pollen. Sixty-nine percent of patients recognizing the single immunodominant T-cell epitope Art v 1(25-36) ...

    Abstract Background: Ninety-five percent of patients with mugwort allergy are sensitized to Art v 1, the sole major allergen in mugwort (Artemisia vulgaris) pollen. Sixty-nine percent of patients recognizing the single immunodominant T-cell epitope Art v 1(25-36) have an HLA-DRB1*01 phenotype.
    Objective: We studied cloning and functional expression of a human alphabeta T-cell receptor (TCR) specific for Art v 1(25-36).
    Methods: TCR chains were RT-PCR amplified from an Art v 1(25-36)-specific T-cell clone, retrovirally transferred, and functionally tested in Jurkat T cells or alternatively in peripheral blood T lymphocytes of nonallergic individuals.
    Results: The alpha-chain of the TCR is composed of TRAV17 and TRAJ45 segments, and the beta-chain uses TRBV18, TRBD1, and TRBJ2-7. Analyses of 23 other Art v 1-specific T-cell clones did not reveal preferential usage of the TRAV17, TRBV18, or other TCR gene families. Efficient TCR transfer into Jurkat T cells was shown by binding of TCR Vbeta18-specific mAb and DRB1*0101/Art v 1 tetramers. Transgenic Jurkat T cells specifically recognized syngeneic EBV B cells pulsed with Art v 1(25-36) peptide and artificial antigen-presenting cells expressing invariant chain::Art v 1 fusion proteins. Moreover, transfer of the TCR into peripheral blood lymphocytes generated T cells that were Art v 1 reactive. Activation of transgenic T cells by artificial antigen-presenting cells was strictly dependent on costimulation.
    Conclusion: For the first time, a detailed molecular and functional analysis of a human allergen-specific TCR is presented.
    MeSH term(s) Allergens/immunology ; Allergens/metabolism ; Amino Acid Sequence ; Antigens, Plant ; B-Lymphocytes ; Base Sequence ; Cell Line ; Cell Line, Transformed ; Cloning, Molecular ; HLA-A Antigens/metabolism ; HLA-DRB1 Chains ; Humans ; Jurkat Cells ; Molecular Sequence Data ; Plant Proteins/metabolism ; Receptors, Antigen, T-Cell, alpha-beta/chemistry ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, alpha-beta/metabolism ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; Transduction, Genetic ; Transgenes
    Chemical Substances Allergens ; Antigens, Plant ; Art v 1 protein, mugwort ; HLA-A Antigens ; HLA-DRB1 Chains ; HLA-DRB1*01:01 antigen ; Plant Proteins ; Receptors, Antigen, T-Cell, alpha-beta
    Language English
    Publishing date 2007-11-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2007.10.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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