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Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination

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The authors thank S. Kolling and the Charité Corona Cross (CCC) Study Group associates J. Schlotterbeck, E. Baysal, T. Panne, F. Legler, M. Girod, B. Bohnen, T. Nguyen, J. Schmitz, R. Klemencic, L. Hintze, N. Avinc, P. Resch, A. Maraj, A. Farghaly, P. Schulz, K. Du, N. Matuschewski, K.Gutwenger, I. Katsianas, Z. Cheng, A. Braginets, G. Janach, and A. Bogdanski for their contributions to donor recruitment, sample processing and measurement and F. Gutsch, T. Bleicker, J. Tesch, P. Tscheak, M. L. Schmidt, and J. Riege for their support. We thank P. Jordan for the illustration of the graphical abstract figure. We thank U. Klein for the critical reading of the manuscript. Funding: This work was funded by the Federal Ministery of Health through a resolution of the German Bundestag (Charité Corona Cross (CCC) and Charité Corona Cross 2.0 (CCC 2.0)). Parts of the work was funded by the German Research Foundation through KFO339 to J.B. and SFB-TR84 projects A4, B6, C8, C10 to L.E.S., A.H., S.H. and B8 to M.A.Ma.; by the European Union’s Horizon 2020 research and innovation program through project RECOVER (GA101003589) to C.D.; the German Ministry of Research through the projects RAPID (01KI1723A) to C.D., A.H., S.H., DZIF (301-4-7-01.703) to C.D., DZL (82DZL0098B1) to M.A. Ma, VARIPath (01KI2021) to V.M.C., RECAST to B.S., M.A.Ma., J.Rö., V.M.C., L.E.S. and NaFoUniMedCovid19 – COVIM, FKZ: 01KX2021 to L.E.S., C.D., V.M.C. and A.T. Author contributions: Conceptualization: L.L., C.G.T., A.T.; Data curation: L.L., J.B., L.H., V.M.C., T.S.; Formal Analysis: L.L., J.B., L.H., F.Ke.; Funding acquisition: A.T.; Investigation: L.L., L.H., J.B.; Resources: B.K., M.D., U.R., F.Ke., M.M., C.U., T.S., F.D., R.L., S.K., J.Ro., K.G., Z.U.-A., M.F., F.Ku., K.S., M.E., S.H., A.H., B.S., S.M., F.P., M.A.Ma., H.W., S.V., M.A.Mu., C.D., N.L., L.M.-A., L.E.S., V.M.C., J.Rö.; Visualization: L.L., J.B., U.R., F.Ke.; Writing: L.L., F.Ke., A.T., C.G.T. Competing interests: The authors L.L., J.B., L.H. and A.T. filed a patent application regarding the usage of flow cytometrically assessed CD3 down-regulation as indicator for functional TCR avidity. L.L. and A.T. filed a patent application regarding S816-830 as dominant cross-reactive T cell epitope. The authors K.S., M.E., U.R. and F.Ke. are employees, H.W. is chief executive officer of JPT. F.K. is co-inventor and co-owner of a patent describing the use of protein-spanning, overlapping peptide pools for detecting antigen-specific T-cells as applied in this study (WO2001063286A2, now expired). F.K. also holds a part-time position as research fellow with the Department of Laboratory Medicine, Medizinische Hochschule Brandenburg, Neuruppin/Germany. S.M. is chief executive officer of Miltenyi Biotec. M.A.Mu. and V.M.C. are named together with Euroimmun GmbH on a patent application filed recently regarding the diagnostic of SARS-CoV-2 by antibody testing. F.P. reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, MedImmune and Novartis unrelated to this work and is member of the steering committee of the OCTIMS study (Novartis). J.R. reports personal fees or grants from Vertex Pharmaceuticals during the conduct of the study. All other authors declare that they have no competing interests. Data and materials availability: All data are available in the main text or in the supplementary materials. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.

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