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  • 1
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    Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-05-25
    Description: Multiple sclerosis (MS) may be an autoimmune disease mediated by T cells specific for a myelin protein. Investigations have demonstrated myelin basic protein (MBP)-reactive T cells that were activated in vivo in MS patients, suggesting that MBP may be a target antigen in MS. The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168). V beta 17 and to a lesser extent V beta 12 were frequently used in recognition of MBP(84-102) among different individuals. In contrast, V beta 17 was very infrequent among lines reactive with MBP (143-168). These data demonstrate shared TCR V beta gene usage for the recognition of immunodominant regions of the human autoantigen MBP. Such TCR structures may be used as targets for specific immunotherapy in MS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wucherpfennig, K W -- Ota, K -- Endo, N -- Seidman, J G -- Rosenzweig, A -- Weiner, H L -- Hafler, D A -- 1 K11 HL 02228-01/HL/NHLBI NIH HHS/ -- NS 00981/NS/NINDS NIH HHS/ -- R01 NS 24247/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 25;248(4958):1016-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1693015" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Blotting, Southern ; Epitopes ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Humans ; Molecular Sequence Data ; Multiple Sclerosis/immunology ; Myelin Basic Protein/*immunology ; Polymerase Chain Reaction ; Receptors, Antigen, T-Cell/*genetics ; Receptors, Antigen, T-Cell, alpha-beta ; T-Lymphocytes/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Common genetic variants modulate pathogen-sensing responses in human dendritic cells (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-03-08
    Description: Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to Escherichia coli lipopolysaccharide, influenza, or interferon-beta (IFN-beta). We localized and validated causal variants to binding sites of pathogen-activated STAT (signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124741/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124741/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Mark N -- Ye, Chun -- Villani, Alexandra-Chloe -- Raj, Towfique -- Li, Weibo -- Eisenhaure, Thomas M -- Imboywa, Selina H -- Chipendo, Portia I -- Ran, F Ann -- Slowikowski, Kamil -- Ward, Lucas D -- Raddassi, Khadir -- McCabe, Cristin -- Lee, Michelle H -- Frohlich, Irene Y -- Hafler, David A -- Kellis, Manolis -- Raychaudhuri, Soumya -- Zhang, Feng -- Stranger, Barbara E -- Benoist, Christophe O -- De Jager, Philip L -- Regev, Aviv -- Hacohen, Nir -- DP1 CA174427/CA/NCI NIH HHS/ -- DP1 MH100706/DP/NCCDPHP CDC HHS/ -- DP1 MH100706/MH/NIMH NIH HHS/ -- DP2 OD002230/OD/NIH HHS/ -- F32 AG043267/AG/NIA NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- R01 AI091568/AI/NIAID NIH HHS/ -- R01 AR063759/AR/NIAMS NIH HHS/ -- R01 DK097768/DK/NIDDK NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- RC2 GM093080/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32 HG002295/HG/NHGRI NIH HHS/ -- U19 AI082630/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1246980. doi: 10.1126/science.1246980.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24604203" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Autoimmune Diseases/genetics ; Communicable Diseases/genetics ; Dendritic Cells/drug effects/*immunology ; Escherichia coli ; Female ; *Gene-Environment Interaction ; Genetic Loci ; Genome-Wide Association Study ; HEK293 Cells ; Host-Pathogen Interactions/*genetics ; Humans ; Influenza A virus ; Interferon Regulatory Factor-7/*genetics ; Interferon-beta/pharmacology ; Lipopolysaccharides/immunology ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; STAT Transcription Factors/*genetics ; Transcriptome ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-08-26
    Description: Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease that serves as an animal model for multiple sclerosis. Oral administration of myelin basic protein (MBP) suppresses EAE by inducing peripheral tolerance. T cell clones were isolated from the mesenteric lymph nodes of SJL mice that had been orally tolerized to MBP. These clones were CD4+ and were structurally identical to T helper cell type 1 (TH1) encephalitogenic CD4+ clones in T cell receptor usage, major histocompatibility complex restriction, and epitope recognition. However, they produced transforming growth factor-beta with various amounts of interleukin-4 and interleukin-10 and suppressed EAE induced with either MBP or proteolipid protein. Thus, mucosally derived TH2-like clones induced by oral antigen can actively regulate immune responses in vivo and may represent a different subset of T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Y -- Kuchroo, V K -- Inobe, J -- Hafler, D A -- Weiner, H L -- AR/A143220/AR/NIAMS NIH HHS/ -- NS29352/NS/NINDS NIH HHS/ -- NS30843/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1994 Aug 26;265(5176):1237-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7520605" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Amino Acid Sequence ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; Clone Cells ; Encephalomyelitis, Autoimmune, Experimental/*immunology ; Epitopes/immunology ; *Immune Tolerance ; Interleukin-10/biosynthesis ; Interleukin-4/biosynthesis ; Lymph Nodes/immunology ; Major Histocompatibility Complex ; Mesentery/immunology ; Mice ; Molecular Sequence Data ; Myelin Basic Protein/administration & dosage/*immunology ; Myelin Proteins/immunology ; Myelin Proteolipid Protein ; Receptors, Antigen, T-Cell/immunology ; Transforming Growth Factor beta/biosynthesis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Effects of oral administration of type II collagen on rheumatoid arthritis (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-09-24
    Description: Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trentham, D E -- Dynesius-Trentham, R A -- Orav, E J -- Combitchi, D -- Lorenzo, C -- Sewell, K L -- Hafler, D A -- Weiner, H L -- AG00294/AG/NIA NIH HHS/ -- MO1 RR01032/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 24;261(5129):1727-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Beth Israel Hospital, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8378772" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Adult ; Aged ; Arthritis, Rheumatoid/*drug therapy/immunology ; Autoimmune Diseases/*drug therapy/immunology ; Collagen/*administration & dosage/adverse effects/therapeutic use ; Double-Blind Method ; Female ; Humans ; Immune Tolerance ; Male ; Middle Aged ; Placebo Effect ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-02-26
    Description: Multiple sclerosis (MS) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system. In a 1-year double-blind study, 30 individuals with relapsing-remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease. Six of 15 individuals in the myelin-treated group had at least one major exacerbation; 12 or 15 had an attack in the control group. T cells reactive with myelin basic protein were reduced in the myelin-treated group. No toxicity or side effects were noted. Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weiner, H L -- Mackin, G A -- Matsui, M -- Orav, E J -- Khoury, S J -- Dawson, D M -- Hafler, D A -- NS23132/NS/NINDS NIH HHS/ -- NS24247/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 26;259(5099):1321-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7680493" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Antigens, Differentiation, T-Lymphocyte/analysis ; Autoantigens/*administration & dosage ; Double-Blind Method ; Female ; HLA-DR2 Antigen/genetics ; Haplotypes ; Humans ; Immune Tolerance ; Male ; Multiple Sclerosis/genetics/*therapy ; Myelin Basic Protein/immunology ; Myelin Sheath/immunology ; Pilot Projects ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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