Project Description
Public­ations

Z02: High-resolution multi-parametric cell and tissue analysis

To unravel the mechanisms of hepatitis virus persistence, TRR179 will employ an interdisciplinary approach. Z2 will provide a central platform for validated, cutting edge immune monitoring and high-speed cell sorting as well as bioinformatics analyses. In addition, Z2 will also develop further these techniques and adapt them to the specific needs of TRR179. In these respects, Z2 will fill technological gaps, provide essential help to harmonize protocols and methods and improve the methods while avoiding parallel and repeated developments. Another major goal of Z2 is to ensure training and education in immune monitoring, cell sorting and bioinformatics for members of this consortium, thus critically contributing also to the IRTG of TRR179.
Su J, Brunner L, Ates Oz E, Sacherl J, Frank G, Kerth HA, Thiele F, Wiegand M, Mogler C, Aguilar JC, Knolle PA, Collin N, Kosinska AD, Protzer U. (2023) Activation of CD4 T cells during prime immunization determines the success of a therapeutic hepatitis B vaccine in HBV-carrier mouse models. J Hepatol. 78(4):717-730. doi: 10.1016/j.jhep.2022.12.013.
Wührl M, Ringelhan M, Ehmer U, Schneider J, Kager J, Lahmer T, Schneider A, Weichert W, Mogler C. (2023) (Seltene) infektiöse Hepatitiden als wichtige Differenzialdiagnose der unklaren Hepatopathie. Pathologie (Heidelb). 44(1):53-62. German. doi: 10.1007/s00292-022-01167-0.
Boettler T, Csernalabics B, Salié H, Luxenburger H, Wischer L, Alizei ES , Zoldan K, Krimmel L, Bronsert P, Schwabenland M, Prinz M, Mogler C, Neumann-Haefelin C, Thimme R, Hofmann M, Bengsch B. (2022) SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis. J Hepatol. 77(3):653-659 https://doi.org/10.1016/j.jhep.2022.03.040.
Schreiber S, Honz M, Mamozai W, Kurktschiev P, Schiemann M, Witter K, Moore E, Zielinski C, Sette A, Protzer U, Wisskirchen K. (2021) Characterization of a library of 20 HBV-specific MHC class II-restricted T cell receptors. Mol Ther Methods Clin Dev. 29;23:476-489. doi: 10.1016/j.omtm.2021.10.012.
Flommersfeld S, Böttcher JP, Ersching J, Flossdorf M, Meiser P, Pachmayr LO, Leube J, Hensel I, Jarosch S, Zhang Q, Zeeshan Chaudhry M, Andrae I, Schiemann M, Busch DH, Cicin-Sain L, Sun JC, Gasteiger G, Victora GD, Höfer T, Buchholz VR, Grassmann S. (2021) Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection.Immunity. 54:2288-2304 e2287. doi: 10.1016/j.immuni.2021.08.002.
Michler T, Kosinska AD, Festag J, Bunse T, Su J, Ringelhan M, Imhof H, Grimm D, Steiger K, Mogler C, Heikenwalder M, Michel ML, Guzman CA, Milstein S, Sepp-Lorenzino L, Knolle P, Protzer U. (2020) Knockdown of Virus Antigen Expression Increases Therapeutic Vaccine Efficacy in High-titer HBV Carrier Mice. Gastroenterology. 158(6):1762-1775.
Winkler F, Bengsch B. (2020) Use of Mass Cytometry to Profile Human T Cell Exhaustion. Front Immunol. 22;10:3039. doi: 10.3389/fimmu.2019.03039.
Andrä I, Ulrich H, Dürr S, Soll D, Henkel L, Angerpointner C, Ritter J, Przibilla S, Stadler H, Effenberger M, Busch DH, Schiemann M. 2020. An Evaluation of T-Cell Functionality After Flow Cytometry Sorting Revealed p38 MAPK Activation. Cytometry A. 97(2):171-183. doi: 10.1002/cyto.a.23964. (Z02)

Smits M, Zoldan K, Ishaque N, Gu Z, Jechow K, Wieland D, Conrad C, Eils R, Fauvelle C, Baumert TF, Emmerich F, Bengsch B, Neumann-Haefelin C, Hofmann M, Thimme R, Boettler T. 2020. Follicular T helper cells shape the HCV-specific CD4 T cell repertoire after viral elimination. J Clin Invest. 130(2):998-1009. (TP01, TP01A, TP02, TP04, Z02)

Schuch A, Salimi Alizei E, Heim K, Wieland D, Kiraithe MM, Kemming J, Llewellyn-Lacey S, Sogukpinar Ö, Ni Y, Urban S, Zimmermann P, Nassal M, Emmerich F, Price DA, Bengsch B, Luxenburger H, Neu-mann-Haefelin C, Hofmann M, Thimme R. 2019. Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load. Gut. 68(5):905-915
Karimzadeh H, Kiraithe MM, Oberhardt V, Salimi Alizei E, Bockmann J, Schulze Zur Wiesch J, Budeus B, Hoffmann D, Wedemeyer H, Cornberg M, Krawczyk A, Rashidi-Alavijeh J, Rodríguez-Frías F, Casillas R, Buti M, Smedile A, Alavian SM, Heinold A, Emmerich F, Panning M, Gostick E, Price DA, Timm J, Hof-mann M, Raziorrouh B, Thimme R, Protzer U, Roggendorf M, Neumann-Haefelin C. 2019. Mutations in Hepatitis D Virus Allow It to Escape Detection by CD8+ T Cells and Evolve at the Population Level. Gast-roenterology. 156(6):1820-1833.
Grassmann S, Pachmayr LO, Leube J, Mihatsch L, Andrae I, Flommersfeld S, Oduro J, Cicin-Sain L, Schiemann M, Flossdorf M, Buchholz VR. 2019. Distinct Surface Expression of Activating Receptor Ly49H Drives Differential Expansion of NK Cell Clones upon Murine Cytomegalovirus Infection. Immuni-ty. 50(6):1391-1400
Steiger K, Ballke S, Yen HY, Seelbach O, Alkhamas A, Boxberg M, Schwamborn K, Knolle PA, Weichert W, Mogler C. 2019. Histopathological research laboratories in translational research: Conception and in-tegration into the infrastructure of pathological institutes. Der Pathologe. 40(2):172-178.
Bengsch B, Ohtani T, Khan O, Setty M, Manne S, O'Brien S, Gherardini PF, Herati RS, Huang AC, Chang KM, Newell EW, Bovenschen N, Pe'er D, Albelda SM, Wherry EJ. 2018a. Epigenomic-Guided Mass Cy-tometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells. Immunity. 48(5):1029-1045.
Bengsch B, Ohtani T, Herati RS, Bovenschen N, Chang KM, Wherry EJ. 2018b. Deep immune profiling by mass cytometry links human T and NK cell differentiation and cytotoxic molecule expression pat-terns. J Immunol Methods. 453:3-10.
Mogler C, König C, Wieland M, Runge A, Besemfelder E, Komljenovic D, Longerich T, Schirmacher P, Augustin HG. 2017. Hepatic stellate cells limit hepatocellular carcinoma progression through the orphan receptor endosialin. EMBO Mol Med. 9(6):741-749.
Wieland E, Rodriguez-Vita J, Liebler SS, Mogler C, Moll I, Herberich SE, Espinet E, Herpel E, Menuchin A, Chang-Claude J, Hoffmeister M, Gebhardt C, Brenner H, Trumpp A, Siebel CW, Hecker M, Utikal J, Sprinzak D, Fischer A. 2017. Endothelial Notch1 Activity Facilitates Metastasis. Cancer Cell. 31(3):355-367
Wisskirchen K, Metzger K, Schreiber S, Asen T, Weigand L, Dargel C, Witter K, Kieback E, Sprinzl MF, Uckert W, Schiemann M, Busch DH, Krackhardt AM, Protzer U. 2017. Isolation and functional characteri-zation of hepatitis B virus-specific T-cell receptors as new tools for experimental and clinical use. PLoS One. 12(8): e0182936
Cossarizza A, Chang HD, Radbruch A, Akdis M, Andrä I, ..., Schiemann M, ..., Yue A, Zhang Q, Zhao Y, Ziegler S, Zimmermann J. 2017. Guidelines for the use of flow cytometry and cell sorting in immunologi-cal studies. Eur J Immunol. 47(10):1584-1797