The response of T lymphocytes plays a critical role in the immune system's fight against SARS-CoV-2, which is a consensus in the scientific and medical communities. But what is the state of antigen-reactive T cells at different sites in the body of COVID-19 patients? And which gene expression changes do they undergo during the course of disease? Little is known about this.
To answer these questions, the researchers applied a new methodological trick, 'reverse phenotyping', based on single-cell analyses of reactive T-cell receptors. Using the reverse phenotyping and integration of this data with single cell RNA-seq data sets obtained from respiratory material from several patient cohorts, it was possible for the first time to determine how the activity state of SARS-COV-2 reactive T cells in the lung changes during the course of the disease. This revealed how SARS-CoV-2 reactive T cell clones differ in the acute phase of infection (with virus still detectable) versus the resolution phase (virus already eliminated).
The novel 'reverse phenotyping' approach used in this study could become a powerful tool for the identification of antigen-reactive T cell receptors. This is important for the rapid development of therapies and vaccines against emergent viruses such as SARS-CoV-2.
This work, initiated by Dr. Kilian Schober (TU Munich) and Dr. Herbert Schiller (ILBD/CPC-M, DZL site Munich), demonstrates once again how the rapid initiation of collaborations between multiple research institutions in this pandemic has led to new insights. Researchers from ILBD/CPC-M, ICB (both Helmholtz Zentrum München), TU München, LMU Klinikum, Asklepios Klinik München-Gauting and Uni Erlangen were involved in the work.
Link to publication: 'Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'' (https://www.nature.com/articles/s41467-021-24730-4)
Original publication: https://www.cpc-munich.de/en/newsevents/news/news/article/28840.html