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Integrated Immunopeptidomic and Proteomic Analysis of COVID-19 lung biopsies

ABSTRACT: Yin S, Klaeger S, Chea VA, Carulli IP, Rachimi S, Black KE, Filbin M, Hariri LP, Knipe RS, Padera RF,Stevens JD, Lane WJ, Carr SA, Wu CJ, Kim EY, and Keskin DB. 2023. Severe respiratory illness is the most prominent manifestation of patients infected with SARS-CoV-2, and yet the molecular mechanisms underlying severe lung disease in COVID-19 affected patients still require elucidation. Human leukocyte antigen class I (HLA-I) expression is crucial for antigen presentation and the host's response to SARS-CoV-2. To gain insights into the immune response and molecular pathways involved in severe lung disease, we performed immunopeptidomic and proteomic analyses of lung tissues recovered at four COVID-19 autopsy and six non-COVID-19 transplants. We found signals of tissue injury and regeneration in lung fibroblast and alveolar type I/II cells, resulting in the production of highly immunogenic self-antigens within the lungs of COVID-19 patients. We also identified immune activation of the M2c macrophage as the primary source of HLA-I presentation and immunogenicity in this context. Additionally, we identified 28 lung signatures that can serve as early plasma markers for predicting infection and severe COVID-19 disease. These protein signatures were predominantly expressed in macrophages and epithelial cells and were associated with complement and coagulation cascades. Our findings emphasize the significant role of macrophage-mediated immunity in the development of severe lung disease in COVID-19 patients.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Sars Coronavirus (ncbitaxon:227859) Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000093012 | MassIVE | Mon Oct 02 07:46:00 BST 2023

SECONDARY ACCESSION(S): PXD045855

REPOSITORIES: MassIVE

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