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.
- 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.
- 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.
- 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.
- 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.
- 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.