Journal
IMMUNITY
Volume 53, Issue 6, Pages 1258-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2020.11.016
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Funding
- German Research Foundation (DFG) [EXC 2167-390884018]
- DFG [433038070, 4096610003]
- COVID-19 research grant from the Land Schleswig-Holstein [DIO002/CoVispecT]
- BMBF Grant AnDiPath [Fkz 03ZZ0838B]
- E-Rare Joint Transnational research support (ERA-Net) [LE3064/2-1]
- BMBF Grant COVIM NaFoUniMedCovid19'' [FKZ: 01KX2021]
- German Ministry of Education and Research [01GM1908A]
- German Federal Ministry of Research and Education
- DFG under Germany's Excellence Strategy, CECAD [EXC 2030 -390661388]
- [RU5042-miTarget]
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CD4 (+) T cells reactive against SARS-CoV-2 can be found in unexposed individuals, and these are suggested to arise in response to common cold coronavirus (CCCoV) infection. Here, we utilized SARS-CoV-2-reactive CD4(+) T cell enrichment to examine the antigen avidity and clonality of these cells, as well as the relative contribution of CCCoV cross-reactivity. SARS-CoV-2-reactive CD4(+) memory T cells were present in virtually all unexposed individuals examined, displaying low functional avidity and multiple, highly variable cross-reactivities that were not restricted to CCCoVs. SARS-CoV-2-reactive CD4 (+) T cells from COVID-1 9 patients lacked cross-reactivity to CCCoVs, irrespective of strong memory T cell responses against CCCoV in all donors analyzed. In severe but not mild COVID-19, SARS-CoV-2-specific T cells displayed low functional avidity and clonality, despite increased frequencies. Our findings identify low-avidity CD4(+) T cell responses as a hallmark of severe COVID-19 and argue against a protective role for CCCoV-reactive T cells in SARS-CoV-2 infection.
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