1. Torque teno viruses exhaust and imprint the human immune system via the HLA-E/NKG2A axis
- Author
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Hannes Vietzen, Cara Simonitsch, Benjamin Friedel, Sarah M. Berger, Laura M. Kühner, Philippe L. Furlano, David M. Florian, Irene Görzer, Maximilian Koblischke, Judith H. Aberle, and Elisabeth Puchhammer-Stöckl
- Subjects
TTV ,Torque teno virus ,NKG2A ,HLA-E ,immune evasion ,immune regulation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The ubiquitous Torque teno virus (TTV) establishes a chronically persistent infection in the human host. TTV has not been associated with any apparent disease, but, as part of the human virome, it may confer a regulatory imprint on the human immune system with as yet unclear consequences. However, so far, only few studies have characterized the TTV-specific immune responses or the overall immunological imprints by TTV. Here, we reveal that TTV infection leads to a highly exhausted TTV-specific CD8+ T-cell response, hallmarked by decreased IFN-γ production and the expression of the inhibitory NKG2A-receptor. On a functional level, we identified a panel of highly polymorphic TTV-encoded peptides that lead to an expansion of regulatory NKG2A+ natural killer, NKG2A+CD4+, and NKG2A+CD8+ T cells via the stabilization of the non-classical HLA-E molecule. Our results thus demonstrate that TTV leads to a distinct imprint on the human immune system that may further regulate overall human immune responses in infectious, autoimmune, and malignant diseases.
- Published
- 2024
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