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

Kathrin Held 1 Latika Bhonsle-Deeng 1 Katherina Siewert 1 Wakiro Sato 1 Eduardo Beltrán 1 Stephan Schmidt 2 Geraldine Rühl 1 Judy Ng 1 Peter Engerer 3 Markus Moser 4 Wolfgang Klinkert 5 Holger Babbe 6 Thomas Misgeld 3, 7, 8, 9 Hartmut Wekerle 5, 7 David-Axel Laplaud 10 Reinhard Hohlfeld 1, 7 Klaus Dornmair 1, 7, *
* Corresponding author
1 Institute of Clinical Neuroimmunology [Munich, Germany]
2 Neurologische Gemeinschaftspraxis [Bonn, Germany]
3 Institute of Neuronal Cell Biology [Munich, Germany]
4 Department for Molecular Medicine [Martinsried, Germany]
5 Department for Neuroimmunology [Martinsried, Germany]
6 Department of Genetics [Boston]
7 SyNergy - Munich Cluster for systems neurology [Munich]
8 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
9 Munich Center for Integrated Protein Science
10 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
Abstract : 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 a and b chains from single CD8 1 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 TCRα and TCRβ 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 Vβ1 1 T-cell population that was strikingly expanded in active brain lesions at clinical onset comprises several subclones expressing distinct yet closely related Vα7.2 1 α chains, including a canonical Vα7.2-Jα33 chain of mucosal-associated invariant T (MAIT) cells. Three other a chains bear striking similarities in their antigen-recognizing, hyper-variable 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 1 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 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.
Keywords : vascular permeability hostdirected immunotherapeutics ANGPTL4 secondary bacterial pneumonia antibiotic resistance
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Kathrin Held, Latika Bhonsle-Deeng, Katherina Siewert, Wakiro Sato, Eduardo Beltrán, et al.. αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell–related features. Neurology Neuroimmunology & Neuroinflammation, American Academy of neurology, 2015, 2 (4), pp.e107. ⟨10.1212/NXI.0000000000000107⟩. ⟨inserm-02146588⟩

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