Increased soluble HLA in COVID-19 present a disease-related, diverse immunopeptidome associated with T cell immunity
Annika Nelde,
Jonas Rieth,
Malte Roerden,
Marissa L. Dubbelaar,
Naomi Hoenisch Gravel,
Jens Bauer,
Reinhild Klein,
Tobias Hoheisel,
Hartmut Mahrhofer,
Siri Göpel,
Michael Bitzer,
Sebastian Hörber,
Andreas Peter,
Jonas S. Heitmann,
Juliane S. Walz
Affiliations
Annika Nelde
Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, 72076 Tübingen, Germany; Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Germany
Jonas Rieth
Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, 72076 Tübingen, Germany; Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany
Malte Roerden
Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Germany; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, 72076 Tübingen, Germany
Marissa L. Dubbelaar
Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, 72076 Tübingen, Germany; Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Germany; Quantitative Biology Center (QBiC), University of Tübingen, 72076 Tübingen, Germany
Naomi Hoenisch Gravel
Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, 72076 Tübingen, Germany; Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Germany
Jens Bauer
Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, 72076 Tübingen, Germany; Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Germany
Reinhild Klein
Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, 72076 Tübingen, Germany
Tobias Hoheisel
Department of Traumatology and Reconstructive Surgery, BG Trauma Center Tübingen, Eberhard Karls University Tübingen, 72076 Tübingen, Germany
Hartmut Mahrhofer
Department of Internal Medicine I, University Hospital Tübingen, 72076 Tübingen, Germany
Siri Göpel
Department of Internal Medicine I, University Hospital Tübingen, 72076 Tübingen, Germany
Michael Bitzer
Department of Internal Medicine I, University Hospital Tübingen, 72076 Tübingen, Germany
Sebastian Hörber
Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72076 Tübingen, Germany
Andreas Peter
Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72076 Tübingen, Germany
Jonas S. Heitmann
Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Germany; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany
Juliane S. Walz
Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, 72076 Tübingen, Germany; Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Germany; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany; Corresponding author
Summary: HLA-presented antigenic peptides are central components of T cell-based immunity in infectious disease. Beside HLA molecules on cell surfaces, soluble HLA molecules (sHLA) are released in the blood suggested to impact cellular immune responses. We demonstrated that sHLA levels were significantly increased in COVID-19 patients and convalescent individuals compared to a control cohort and positively correlated with SARS-CoV-2-directed cellular immunity. Of note, patients with severe courses of COVID-19 showed reduced sHLA levels. Mass spectrometry-based characterization of sHLA-bound antigenic peptides, the so-called soluble immunopeptidome, revealed a COVID-19-associated increased diversity of HLA-presented peptides and identified a naturally presented SARS-CoV-2-derived peptide from the viral nucleoprotein in the plasma of COVID-19 patients. Of interest, sHLA serum levels directly correlated with the diversity of the soluble immunopeptidome. Together, these findings suggest an inflammation-driven release of sHLA in COVID-19, directly influencing the diversity of the soluble immunopeptidome with implications for SARS-CoV-2-directed T cell-based immunity and disease outcome.
