ArticleNeurology(R) neuroimmunology & neuroinflammation2015
αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell-related features.
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Article in Neurology(R) neuroimmunology & neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
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33 citing papers in PubMed, 53 citations in OpenAlex.
- Early adaptive immune activation detected in monozygotic twins with prodromal multiple sclerosis.The Journal of clinical investigation · 2019Trial
- Biological functions and therapeutic applications of human mucosal-associated invariant T cells.Journal of biomedical science · 2025Review
- Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis.Nature communications · 2024Article
- A Comprehensive Investigation of Stimulatory Agents on MAIT and Vα7.2+/CD161- T Cell Response and Effects of Immunomodulatory Drugs.International journal of molecular sciences · 2024Article
- Investigating Vα7.2International journal of molecular sciences · 2024Article
- Article
- Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Unconventional T cells in brain homeostasis, injury and neurodegeneration.Frontiers in immunology · 2023Review
- The immunology of multiple sclerosis.Nature reviews. Immunology · 2022Review
- Does Dementia Have a Microbial Cause?NeuroSci · 2022Review
- MAIT Cells and Microbiota in Multiple Sclerosis and Other Autoimmune Diseases.Microorganisms · 2021Review
- The Nerves to Conduct a Multiple Sclerosis Crime Investigation.International journal of molecular sciences · 2021Review
- The contribution of thymic tolerance to central nervous system autoimmunity.Seminars in immunopathology · 2021Review
- Teriflunomide Treatment of Multiple Sclerosis Selectively Modulates CD8 Memory T Cells.Frontiers in immunology · 2021Article
- Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections.Frontiers in immunology · 2021Article
- The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis.Frontiers in immunology · 2021Review
- Thymic Involution and Altered Naive CD4 T Cell Homeostasis in Neuromyelitis Optica Spectrum Disorder.Frontiers in immunology · 2021Article
- Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Dimethylfumarate.Frontiers in neurology · 2021Article
- Brain astrocytes and microglia express functional MR1 molecules that present microbial antigens to mucosal-associated invariant T (MAIT) cells.Journal of neuroimmunology · 2020Article
- Smad7 in intestinal CD4Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
17 authors at 6 institutions in 2 countries.
Kathrin HeldInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Latika Bhonsle-DeengInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Katherina SiewertInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Wakiro SatoInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Eduardo BeltránInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Stephan SchmidtInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Geraldine RühlInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Judy K M NgInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Peter EngererInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Markus MoserInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Wolfgang E F KlinkertInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Holger BabbeInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Thomas MisgeldInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Hartmut WekerleInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
David-Axel LaplaudInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Reinhard HohlfeldInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Klaus DornmairInstitute of Clinical Neuroimmunology (K.H., L.B.-D., K.S., W.S., E.B., G.R., J.K.M.N., R.H., K.D.), Ludwig-Maximilians University, Munich, Germany; Neurologische Gemeinschaftspraxis (S.S.), Gesundheitszentrum St. Johannes Hospital, Bonn, Germany; Institute of Neuronal Cell Biology (P.E., T.M.), TU Munich, Munich, Germany; Department for Molecular Medicine (M.M.), Max-Planck-Institute of Biochemistry, Martinsried, Germany; Department for Neuroimmunology (W.E.F.K., H.W.), Max-Planck-Institute of Neurobiology, Martinsried, Germany; Department of Genetics (H.B.), Harvard Medical School, Boston, MA; Munich Cluster for Systems Neurology (SyNergy) (T.M., H.W., R.H., K.D.), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) and Center for Integrated Protein Science (CIPSM) (T.M.), Munich, Germany; and INSERM, UMR 1064 (D.A.L.), Nantes, France.
Max Planck Institute of Biochemistry · DEMunich Cluster for Systems Neurology · DECenter for Integrated Protein Science Munich · DEGerman Center for Neurodegenerative Diseases · DEMax Planck Institute of Neurobiology · DEHarvard University · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo characterize phenotypes of T cells that accumulated in multiple sclerosis (MS) lesions, to compare the lesional T-cell receptor (TCR) repertoire of T-cell subsets to peripheral blood, and to identify paired α and β chains from single CD8(+) T cells from an index patient who we followed for 18 years.
methodsWe combined immunohistochemistry, laser microdissection, and single-cell multiplex PCR to characterize T-cell subtypes and identify paired TCRα and TCRβ chains from individual brain-infiltrating T cells in frozen brain sections. The lesional and peripheral TCR repertoires were analyzed by pyrosequencing.
resultsWe found that a TCR Vβ1(+) T-cell population that was strikingly expanded in active brain lesions at clinical onset comprises several subclones expressing distinct yet closely related Vα7.2(+) α chains, including a canonical Vα7.2-Jα33 chain of mucosal-associated invariant T (MAIT) cells. Three other α chains bear striking similarities in their antigen-recognizing, hypervariable complementarity determining region 3. Longitudinal repertoire studies revealed that the TCR chains that were massively expanded in brain at onset persisted for several years in blood or CSF but subsequently disappeared except for the canonical Vα7.2(+) MAIT cell and a few other TCR sequences that were still detectable in blood after 18 years.
conclusionsOur observation that a massively expanded TCR Vβ1-Jβ2.3 chain paired with distinct yet closely related canonical or atypical MAIT cell-related α chains strongly points to an antigen-driven process in early active MS brain lesions.
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