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      Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

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          Summary

          Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8 + and CD4 + T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4 + T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4 + response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8 + T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4 + T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.

          Highlights

          • Measuring immunity to SARS-CoV-2 is key for understanding COVID19 and vaccine development

          • Epitope pools detect CD4 + and CD8 + T cells in 100 and 70% of convalescent COVID patients

          • T cell responses are focused not only on spike but also on M, N and other ORFs

          • T cell reactivity to SARS-CoV-2 epitopes is also detected in non-exposed individuals

          Abstract

          An analysis of immune cell responses to SARS-CoV-2 from recovered patients identifies the regions of the virus that is targeted and also reveals cross-reactivity with other common circulating coronaviruses

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          Author and article information

          Contributors
          Journal
          Cell
          Cell
          Cell
          Elsevier Inc.
          0092-8674
          1097-4172
          20 May 2020
          20 May 2020
          Affiliations
          [1 ]Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
          [2 ]Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
          [3 ]Department of Microbiology and Immunology, University of North Carolina School of Medicine, USA
          [4 ]Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York
          Author notes
          [∗∗ ]Corresponding author alex@ 123456lji.org shane@ 123456lji.org
          [∗]

          indicates equal contributions

          Article
          S0092-8674(20)30610-3
          10.1016/j.cell.2020.05.015
          7237901
          32473127
          0d075e00-eff9-4a61-bd0e-e8b1f56abc80
          © 2020 Elsevier Inc.

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          : 20 April 2020
          : 4 May 2020
          : 7 May 2020
          Categories
          Article

          Cell biology
          Cell biology

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