[PDF][PDF] Low-avidity CD4+ T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19

P Bacher, E Rosati, D Esser, GR Martini, C Saggau… - Immunity, 2020 - cell.com
P Bacher, E Rosati, D Esser, GR Martini, C Saggau, E Schiminsky, J Dargvainiene…
Immunity, 2020cell.com
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 …
Summary
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-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+ 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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