αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell-related features

Autor: Katherina Siewert, Hartmut Wekerle, Latika Bhonsle-Deeng, Klaus Dornmair, Eduardo Beltrán, Wakiro Sato, Thomas Misgeld, David-Axel Laplaud, Geraldine Rühl, Stephan Schmidt, Holger Babbe, Markus Moser, Reinhard Hohlfeld, Peter Engerer, Judy K.M. Ng, Wolfgang E. F. Klinkert, Kathrin Held
Přispěvatelé: Institute of Clinical Neuroimmunology [Munich, Germany], Ludwig-Maximilians-Universität München (LMU), Neurologische Gemeinschaftspraxis [Bonn, Germany], Gesundheitszentrum St. Johannes Hospital [Bonn, Germany], Institute of Neuronal Cell Biology [Munich, Germany], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Department for Molecular Medicine [Martinsried, Germany], Max-Planck-Institut für Biogeochemie (MPI-BGC), Department for Neuroimmunology [Martinsried, Germany], Max-Planck-Institute of Neurobiology [Martinsried, Germany], Department of Genetics [Boston], Harvard Medical School [Boston] (HMS), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), This research was supported by Cooperative Basic Research Grant NMRC/CBRG/ 0030/2013 and National Health Innovation Centre Grant NHIC-I2D-1509081 from the National Medical Research Council, Singapore, to N.S.T. and V.T.K.C., respectively. L.Y. is supported by Start-Up Grant Y01416206 from Southern University of Science and Technology (SUSTech). L.L.’s contributions were supported by the National Natural Science Foundation of China (81771617). A grant by the French National Research Agency (ANR-11-LABX-0021-01-LipSTIC LabEx) is also acknowledged. The mouse strain used (C57/B6, 129S5-Angptl4Gt(OST352973)Lex/Mmucd, identification no. 032147-UCD) was obtained from the Mutant Mouse Regional Resource Center (MMRRC), an NIHfunded strain repository, and was donated to the MMRRC by Genentech, Inc., ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), Le Bihan, Sylvie, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Ludwig-Maximilians University [Munich] (LMU), Max-Planck-Institute of Biochemistry [Martinsried, Germany], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München), ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Neurology Neuroimmunology & Neuroinflammation
Neurology Neuroimmunology & Neuroinflammation, 2015, 2 (4), pp.e107. ⟨10.1212/NXI.0000000000000107⟩
Neurology Neuroimmunology & Neuroinflammation, American Academy of neurology, 2015, 2 (4), pp.e107. ⟨10.1212/NXI.0000000000000107⟩
Neurology® Neuroimmunology & Neuroinflammation
Neurology 2(4), e107 (2015). doi:10.1212/NXI.0000000000000107
ISSN: 2332-7812
Popis: OBJECTIVES: To 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 alpha and beta chains from single CD8(+) T cells from an index patient who we followed for 18 years.; METHODS: We combined immunohistochemistry, laser microdissection, and single-cell multiplex PCR to characterize T-cell subtypes and identify paired TCRalpha and TCRbeta chains from individual brain-infiltrating T cells in frozen brain sections. The lesional and peripheral TCR repertoires were analyzed by pyrosequencing.; RESULTS: We found that a TCR Vbeta1(+) T-cell population that was strikingly expanded in active brain lesions at clinical onset comprises several subclones expressing distinct yet closely related Valpha7.2(+) alpha chains, including a canonical Valpha7.2-Jalpha33 chain of mucosal-associated invariant T (MAIT) cells. Three other alpha 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 Valpha7.2(+) MAIT cell and a few other TCR sequences that were still detectable in blood after 18 years.; CONCLUSIONS: Our observation that a massively expanded TCR Vbeta1-Jbeta2.3 chain paired with distinct yet closely related canonical or atypical MAIT cell-related alpha chains strongly points to an antigen-driven process in early active MS brain lesions.
Databáze: OpenAIRE
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