T cell cross-reactivity in autoimmune-like hepatitis triggered by COVID-19

The study, titled “T cell cross-reactivity in autoimmune-like hepatitis triggered by COVID-19” presents a significant finding in understanding how COVID-19 may trigger autoimmune responses, specifically autoimmune-like hepatitis.

Here’s a detailed summary:


  • The study investigates the hypothesis that SARS-CoV-2 infection or vaccination can lead to the expansion of T cells carrying T cell receptors (TCRs) that recognize self-antigens, potentially causing autoimmune-like hepatitis.

Key Elements:

  1. Background: The study begins by noting the increase in pediatric hepatitis cases of unknown etiology and its potential link to SARS-CoV-2 infection or vaccination.
  2. Research Hypothesis: It hypothesizes that TCRs, known to distinguish between self- and non-self antigens but also exhibit cross-reactivity, might expand following SARS-CoV-2 exposure, recognizing self-antigens and potentially leading to autoimmune-like hepatitis.
  3. Methodology:
    • TCR repertoire sequencing data were analyzed to identify TCRs that recognize self-antigens following SARS-CoV-2 infection.
    • The analysis included cross-referencing TCR binding datasets (VDJdb and ImmuneCODE) to find TCRs with similar sequences that may recognize the same antigen.
  4. Findings:
    • The study identified TCRs that showed cross-reactivity with T cell epitopes derived from SARS-CoV-2, Epstein–Barr virus (EBV), and/or the human proteome.
    • Specific TCR sequences were found to be significantly increased in frequency in COVID-19 patients, suggesting clonal expansion.
    • One particular TCR (CoV-TCR) was identified that recognizes a self-peptide derived from ABCD3, a peroxisomal membrane protein abundant in hepatocytes.
    • This TCR did not recognize a previously reported SARS-CoV-2 antigenic peptide but might recognize other SARS-CoV-2 antigenic peptides not yet identified.
  5. Implications:
    • The study supports the idea that clonally expanded T cells with cross-reactivity could be one of the causes of COVID-19-related autoimmune-like hepatitis.
    • It highlights the need for comprehensive research to further explore this possibility.


  • This research offers a new perspective on how COVID-19 might trigger autoimmune responses, particularly autoimmune-like hepatitis. The identification of specific TCRs that recognize self-antigens post-COVID-19 infection or vaccination is a significant step in understanding the pathophysiology of such autoimmune conditions.

Read More: https://www.sciencedirect.com/science/article/pii/S2949928323000093

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