tetano
Editor, Senior Moderator
Immunity
. 2020 Nov 26;S1074-7613(20)30503-3.
doi: 10.1016/j.immuni.2020.11.016. Online ahead of print.
Low-Avidity CD4 [SUP]+[/SUP] T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19
Petra Bacher[SUP] 1 [/SUP], Elisa Rosati[SUP] 2 [/SUP], Daniela Esser[SUP] 3 [/SUP], Gabriela Rios Martini[SUP] 4 [/SUP], Carina Saggau[SUP] 5 [/SUP], Esther Schiminsky[SUP] 5 [/SUP], Justina Dargvainiene[SUP] 3 [/SUP], Ina Schr?der[SUP] 3 [/SUP], Imke Wieters[SUP] 6 [/SUP], Yascha Khodamoradi[SUP] 6 [/SUP], Fabian Eberhardt[SUP] 6 [/SUP], Maria J G T Vehreschild[SUP] 6 [/SUP], Holger Neb[SUP] 7 [/SUP], Michael Sonntagbauer[SUP] 7 [/SUP], Claudio Conrad[SUP] 8 [/SUP], Florian Tran[SUP] 9 [/SUP], Philip Rosenstiel[SUP] 2 [/SUP], Robert Markewitz[SUP] 3 [/SUP], Klaus-Peter Wandinger[SUP] 3 [/SUP], Max Augustin[SUP] 10 [/SUP], Jan Rybniker[SUP] 10 [/SUP], Matthias Kochanek[SUP] 11 [/SUP], Frank Leypoldt[SUP] 12 [/SUP], Oliver A Cornely[SUP] 13 [/SUP], Philipp Koehler[SUP] 14 [/SUP], Andre Franke[SUP] 2 [/SUP], Alexander Scheffold[SUP] 5 [/SUP]
Affiliations
Abstract
CD4[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] T cells from COVID-19 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[SUP]+[/SUP] 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.
Keywords: ARTE; COVID-19; SARS-CoV-2; T cell cross-reactivity; antigen-reactive T cell enrichment; antigen-specific T cells; common cold coronavirus; human coronavirus; pre-existing memory.
. 2020 Nov 26;S1074-7613(20)30503-3.
doi: 10.1016/j.immuni.2020.11.016. Online ahead of print.
Low-Avidity CD4 [SUP]+[/SUP] T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19
Petra Bacher[SUP] 1 [/SUP], Elisa Rosati[SUP] 2 [/SUP], Daniela Esser[SUP] 3 [/SUP], Gabriela Rios Martini[SUP] 4 [/SUP], Carina Saggau[SUP] 5 [/SUP], Esther Schiminsky[SUP] 5 [/SUP], Justina Dargvainiene[SUP] 3 [/SUP], Ina Schr?der[SUP] 3 [/SUP], Imke Wieters[SUP] 6 [/SUP], Yascha Khodamoradi[SUP] 6 [/SUP], Fabian Eberhardt[SUP] 6 [/SUP], Maria J G T Vehreschild[SUP] 6 [/SUP], Holger Neb[SUP] 7 [/SUP], Michael Sonntagbauer[SUP] 7 [/SUP], Claudio Conrad[SUP] 8 [/SUP], Florian Tran[SUP] 9 [/SUP], Philip Rosenstiel[SUP] 2 [/SUP], Robert Markewitz[SUP] 3 [/SUP], Klaus-Peter Wandinger[SUP] 3 [/SUP], Max Augustin[SUP] 10 [/SUP], Jan Rybniker[SUP] 10 [/SUP], Matthias Kochanek[SUP] 11 [/SUP], Frank Leypoldt[SUP] 12 [/SUP], Oliver A Cornely[SUP] 13 [/SUP], Philipp Koehler[SUP] 14 [/SUP], Andre Franke[SUP] 2 [/SUP], Alexander Scheffold[SUP] 5 [/SUP]
Affiliations
- PMID: 33296686
- DOI: 10.1016/j.immuni.2020.11.016
Abstract
CD4[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] T cells from COVID-19 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[SUP]+[/SUP] 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.
Keywords: ARTE; COVID-19; SARS-CoV-2; T cell cross-reactivity; antigen-reactive T cell enrichment; antigen-specific T cells; common cold coronavirus; human coronavirus; pre-existing memory.