| Autor: |
Tso, Alexandria, Veizades, Stefan, Jensen, Annie, Huang, Xianxi, DAddabbo, Jessica, Sasagawa, Koki, Chien, Yu-Hsiu, Roy Chowdhury, Roshni, Chan, Charles, Davis, Mark, Nguyen, Patricia |
| Zdroj: |
Arteriosclerosis, Thrombosis, and Vascular Biology (Ovid); May 2022, Vol. 42 Issue: Supplement 1 pA504-A504, 1p |
| Abstrakt: |
Background:Vascular thrombosis has been described in patients actively infected with influenza and, more recently, with the coronavirus. The risk may persist during the convalescence period. The underlying mechanisms mediating these events remain unclear.Objective:To determine whether human coronary plaque T cells reactive to influenza virus are also activated by self-proteins.Methods/Results:Using single cell targetRNAseq, we mapped the T cell repertoire in 19 patients with a range of coronary artery disease severity. To determine the potential peptides activating coronary plaque T cell receptors (TCRs), we matched TCR alpha and beta identity with HLA restriction to a database of known specificities. We found that plaque TCRs were potentially activated by viral epitopes, including those from the influenza M1 protein. We used a computational algorithm to identify self-proteins in the endothelial cells and vascular smooth muscle cells that may have peptides with similar homologies to viral epitopes predicted to bind our plaque TCRs. We then introduced plaque TCRs into the Jurkat T cells, exposed these cells to T2 (HLA-2 antigen presenting cells), viral peptides (e.g., M1) and self-epitopes (e.g., TSPAN17; ZIP9), and demonstrated T cell cross reactivity in vitro (Figure 1). TSPAN17 is a transmembrane protein that regulates VE-cadherin expression and promotes T cell transmigration. Zip9, in contrast, is a protein that regulates zinc homeostasis, serves as an androgen receptor on endothelial cells, and has been shown to promote endothelial proliferation.Conclusion:Taken together, our findings suggest that T cell cross reactivity may be a potential mediator of viral-induced arterial thrombosis. |
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