Author: Simnica, Donjete; Schultheiß, Christoph; Mohme, Malte; Paschold, Lisa; Willscher, Edith; Fitzek, Antonia; Püschel, Klaus; Matschke, Jakob; Ciesek, Sandra; Sedding, Daniel G; Zhao, Yu; Gagliani, Nicola; Maringer, Yacine; Walz, Juliane S; Heide, Janna; Schulzeâ€zurâ€Wiesch, Julian; Binder, Mascha
Title: Landscape of Tâ€cell repertoires with public COVIDâ€19â€associated Tâ€cell receptors in preâ€pandemic risk cohorts Cord-id: 3uzb4v9e Document date: 2021_8_28
ID: 3uzb4v9e
Snippet: OBJECTIVES: T cells have an essential role in the antiviral defence. Public Tâ€cell receptor (TCR) clonotypes are expanded in a substantial proportion of COVIDâ€19 patients. We set out to exploit their potential use as readâ€out for COVIDâ€19 Tâ€cell immune responses. METHODS: We searched for COVIDâ€19â€associated Tâ€cell clones with public TCRs, as defined by identical complementarityâ€determining region 3 (CDR3) beta chain amino acid sequence that can be reproducibly detected in the b
Document: OBJECTIVES: T cells have an essential role in the antiviral defence. Public Tâ€cell receptor (TCR) clonotypes are expanded in a substantial proportion of COVIDâ€19 patients. We set out to exploit their potential use as readâ€out for COVIDâ€19 Tâ€cell immune responses. METHODS: We searched for COVIDâ€19â€associated Tâ€cell clones with public TCRs, as defined by identical complementarityâ€determining region 3 (CDR3) beta chain amino acid sequence that can be reproducibly detected in the blood of COVIDâ€19 patients. Of the different clonotype identification algorithms used in this study, deep sequencing of brain tissue of five patients with fatal COVIDâ€19 delivered 68 TCR clonotypes with superior representation across 140 immune repertoires of unrelated COVIDâ€19 patients. RESULTS: Mining of immune repertoires from subjects not previously exposed to the virus showed that these clonotypes can be found in almost 20% of preâ€pandemic immune repertoires of healthy subjects, with lower representation in repertoires from risk groups like individuals above the age of 60 years or patients with cancer. CONCLUSION: Together, our data show that at least a proportion of the SARSâ€CoVâ€2 Tâ€cell response is mediated by public TCRs that are present in repertoires of unexposed individuals. The lower representation of these clones in repertoires of risk groups or failure to expand such clones may contribute to more unfavorable clinical COVIDâ€19 courses.
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