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. Graphical Abstract Highlights • Low avidity and broad cross-reactivities of pre-existing SARS-CoV-2 memory T cells • Strong CCCoV-specific memory CD4 + T cell responses in all analyzed individuals • SARS-CoV-2-specific CD4 + T cells in COVID-19 patients lack cross-reactivity to CCCoVs • Low avidity and clonality of SARS-CoV-2-specific T cell responses in severe COVID-19 Bacher et al. identify excessive but low-avidity T cell responses to SARS-CoV-2 as a hallmark of severe but not mild COVID-19. Pre-existing memory to SARS-CoV-2 in unexposed donors also displayed low avidity and harbored multiple, highly variable cross-reactivities that were not restricted to common cold coronaviruses.
【저자키워드】 COVID-19, SARS-CoV-2, Antigen-specific T cells, common cold coronavirus, T cell cross-reactivity, antigen-reactive T cell enrichment, human coronavirus, ARTE, pre-existing memory,