Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients

Christa Lichtensteiger; Maximilian Koblischke; Fiamma Berner; Ann-Kristin Jochum; Tobias Sinnberg; Beatrice Balciunaite; Mette-Triin Purde; Vincent Walter; Marie-Therese Abdou; Kathrin Hofmeister; Philipp Kohler; Pietro Vernazza; Werner C Albrich; Christian R Kahlert; Alexander Zoufaly; Marianna T Traugott; Lukas Kern; Urs Pietsch; Gian-Reto Kleger; Miodrag Filipovic; Manfred Kneilling; Antonio Cozzio; Oltin Pop; David Bomze; Andreas Bergthaler; Omar Hasan Ali; Judith Aberle; Lukas Flatz

doi:10.1016/j.jaut.2023.103118

Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients

J Autoimmun. 2023 Oct 10:140:103118. doi: 10.1016/j.jaut.2023.103118. Online ahead of print.

Authors

Christa Lichtensteiger¹, Maximilian Koblischke², Fiamma Berner¹, Ann-Kristin Jochum³, Tobias Sinnberg⁴, Beatrice Balciunaite⁵, Mette-Triin Purde¹, Vincent Walter⁵, Marie-Therese Abdou¹, Kathrin Hofmeister⁵, Philipp Kohler⁶, Pietro Vernazza⁶, Werner C Albrich⁶, Christian R Kahlert⁶, Alexander Zoufaly⁷, Marianna T Traugott⁸, Lukas Kern⁹, Urs Pietsch¹⁰, Gian-Reto Kleger¹¹, Miodrag Filipovic¹⁰, Manfred Kneilling¹², Antonio Cozzio¹³, Oltin Pop¹, David Bomze¹⁴, Andreas Bergthaler¹⁵, Omar Hasan Ali¹⁶, Judith Aberle², Lukas Flatz¹⁷

Affiliations

¹ Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
² Center for Virology, Medical University of Vienna, Vienna, Austria.
³ Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Insitute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
⁴ Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) Image-Guided and Functionally Instructed Tumor Therapies, Eberhard Karls University Hospital Tübingen, Tübingen, Germany.
⁵ Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany.
⁶ Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
⁷ Department of Medicine IV, Clinic Favoriten, Vienna Healthcare Group, Vienna, Austria; Faculty of Medicine, Sigmund Freud University Vienna, Austria.
⁸ Department of Medicine IV, Clinic Favoriten, Vienna Healthcare Group, Vienna, Austria.
⁹ Department of Pneumology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
¹⁰ Surgical Intensive Care Unit, Division of Anaesthesiology, Intensive Care, Rescue and Pain Medicine, Kantonsspital St. Gallen, Switzerland.
¹¹ Division of Intensive Care Medicine, Kantonsspital St. Gallen, Switzerland.
¹² Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) Image-Guided and Functionally Instructed Tumor Therapies, Eberhard Karls University Hospital Tübingen, Tübingen, Germany; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Germany.
¹³ Department of Dermatology, Venereology and Allergology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
¹⁴ Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Sackler Faculty of Medicine, Tel Aviv University; Tel Aviv, Israel.
¹⁵ Institute for Hygiene and Applied Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria; CeMM Research Center for Molecular Medicine or the Austrian Academy of Sciences, Vienna, Austria.
¹⁶ Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
¹⁷ Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany; Department of Dermatology, Venereology and Allergology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland. Electronic address: lukas.flatz@med.uni-tuebingen.de.

PMID: 37826919
DOI: 10.1016/j.jaut.2023.103118

Abstract

Background: The role of autoreactive T cells on the course of Coronavirus disease-19 (COVID-19) remains elusive. Type II pneumocytes represent the main target cells of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autoimmune responses against antigens highly expressed in type II pneumocytes may influence the severity of COVID-19 disease.

Objective: The aim of this study was to investigate autoreactive T cell responses against self-antigens highly expressed in type II pneumocytes in the blood of COVID-19 patients with severe and non-severe disease.

Methods: We collected blood samples of COVID-19 patients with varying degrees of disease severity and of pre-pandemic controls. T cell stimulation assays with peptide pools of type II pneumocyte antigens were performed in two independent cohorts to analyze the autoimmune T cell responses in patients with non-severe and severe COVID-19 disease. Target cell lysis assays were performed with lung cancer cell lines to determine the extent of cell killing by type II PAA-specific T cells.

Results: We identified autoreactive T cell responses against four recently described self-antigens highly expressed in type II pneumocytes, known as surfactant protein A, surfactant protein B, surfactant protein C and napsin A, in the blood of COVID-19 patients. These antigens were termed type II pneumocyte-associated antigens (type II PAAs). We found that patients with non-severe COVID-19 disease showed a significantly higher frequency of type II PAA-specific autoreactive T cells in the blood when compared to severely ill patients. The presence of high frequencies of type II PAA-specific T cells in the blood of non-severe COVID-19 patients was independent of their age. We also found that napsin A-specific T cells from convalescent COVID-19 patients could kill lung cancer cells, demonstrating the functional and cytotoxic role of these T cells.

Conclusions: Our data suggest that autoreactive type II PAA-specific T cells have a protective role in SARS-CoV-2 infections and the presence of high frequencies of these autoreactive T cells indicates effective viral control in COVID-19 patients. Type II-PAA-specific T cells may therefore promote the killing of infected type II pneumocytes and viral clearance.

Keywords: Autoantigen; Autoimmunity; COVID-19; SARS-CoV-2; type II pneumocyte.