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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE (Open Access)

An autoantigen profile from Jurkat T-Lymphoblasts provides a molecular guide for investigating autoimmune sequelae of COVID-19

Julia Y. Wang https://orcid.org/0000-0002-9458-5825 A * , Wei Zhang B , Michael W. Roehrl A , Victor B. Roehrl A and Michael H. Roehrl https://orcid.org/0000-0003-4892-1098 C D *
+ Author Affiliations
- Author Affiliations

A Curandis, Boston, MA, USA.

B Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guizhou, China.

C Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

D Harvard Medical School, Boston, MA, USA.


Handling Editor: John Wade

Australian Journal of Chemistry 76(8) 508-524 https://doi.org/10.1071/CH22268
Submitted: 20 December 2022  Accepted: 6 June 2023   Published: 20 July 2023

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY)

Abstract

In order to understand autoimmune phenomena contributing to the pathophysiology of COVID-19 and post-COVID syndrome, we have been profiling autoantigens (autoAgs) from various cell types. Although cells share numerous autoAgs, each cell type gives rise to unique COVID-altered autoAg candidates, which may explain the wide range of symptoms experienced by patients with autoimmune sequelae of SARS-CoV-2 infection. Based on the unifying property of affinity between autoAgs and the glycosaminoglycan dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of human Jurkat T-cells, of which at least 105 (75%) are known targets of autoantibodies. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) DS-affinity proteins are altered at protein and/or RNA levels in SARS-CoV-2-infected cells or patients, with at least 94 being known autoAgs in a wide spectrum of autoimmune diseases and cancer. Protein alterations by ubiquitination and phosphorylation during the viral infection are major contributors of autoAgs. The autoAg protein network is significantly associated with cellular response to stress, apoptosis, RNA metabolism, mRNA processing and translation, protein folding and processing, chromosome organization, cell cycle, and muscle contraction. The autoAgs include clusters of histones, CCT/TriC chaperonin, DNA replication licensing factors, proteasome and ribosome proteins, heat shock proteins, serine/arginine-rich splicing factors, 14-3-3 proteins, and cytoskeletal proteins. AutoAgs, such as LCP1 and NACA, that are altered in the T cells of COVID patients may provide insight into T-cell responses to viral infection and merit further study. The autoantigen-ome from this study contributes to a comprehensive molecular map for investigating acute, subacute, and chronic autoimmune disorders caused by SARS-CoV-2.

Keywords: autoantibodies, autoantigens, autoimmunity, COVID-19, long COVID, dermatan sulfate, SARS-Cov-2, T cell immunity.

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