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Cross-Reactive and Mono-Reactive SARS-CoV-2 CD4+ T Cells in Prepandemic and COVID-19 Convalescent Individuals

63 Pages Posted: 30 Jun 2021 Publication Status: Review Complete

See all articles by Alexandra M. Johansson

Alexandra M. Johansson

Benaroya Research Institute at Virginia Mason

Uma Malhotra

Benaroya Research Institute at Virginia Mason

Yeseul G. Kim

Benaroya Research Institute at Virginia Mason

Rebecca Gomez

Benaroya Research Institute at Virginia Mason

Maxwell P. Krist

University of Washington - Department of Medicine

Anna Wald

University of Washington - Department of Medicine; Division of Allergy and Infectious Diseases, University of Washington

David M. Koelle

Benaroya Research Institute at Virginia Mason

William Kwok

Benaroya Research Institute at Virginia Mason

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Abstract

Class II tetramer reagents were used to identify SARS-CoV-2-specific CD4+ T cell epitopes and study these epitope-specific T cells ex vivo. Dominant and subdominant epitopes were identified. Majority of epitopes identified have <67% amino acid sequence identity with endemic coronaviruses and are unlikely to elicit cross-reactive T cell responses. However, four Spike epitopes highly homologous with endemic coronaviruses were identified. Specific T cells for three such DR-restricted epitopes were present at relatively low frequencies in convalescent individuals. Spike cross-reactive memory T cells that recognized a DPB1*04:01 restricted epitope were detected in uninfected DPB1*04:01 persons at low frequencies, with higher frequencies and different phenotypes in convalescent persons. Patterns of T cell cross-reactivity between SARS-CoV-2 and endemic coronaviruses differed amongst DPB1*04:01 persons. Spike cross-reactive T cells expanded to a lesser extent compared to mono-reactive T cells in these individuals and only contributed a small proportion of the overall Spike-specific CD4+ T cells.

Funding Information: Funding was provided from NIH grants 3U19AI135817-04S1 (WWK), 1R21AI163999 (DMK) and NIH contract HHSN75N93019C00063 (DMK).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: The study was approved by Benaroya Research Institute and University of Washington Institutional Review Boards and all blood samples were obtained with informed consent from the participants.

Suggested Citation

Johansson, Alexandra M. and Malhotra, Uma and Kim, Yeseul G. and Gomez, Rebecca and Krist, Maxwell P. and Wald, Anna and Koelle, David M. and Kwok, William, Cross-Reactive and Mono-Reactive SARS-CoV-2 CD4+ T Cells in Prepandemic and COVID-19 Convalescent Individuals. Available at SSRN: https://ssrn.com/abstract=3877561 or http://dx.doi.org/10.2139/ssrn.3877561
This version of the paper has not been formally peer reviewed.

Alexandra M. Johansson

Benaroya Research Institute at Virginia Mason

United States

Uma Malhotra

Benaroya Research Institute at Virginia Mason ( email )

United States

Yeseul G. Kim

Benaroya Research Institute at Virginia Mason

United States

Rebecca Gomez

Benaroya Research Institute at Virginia Mason

United States

Maxwell P. Krist

University of Washington - Department of Medicine

Seattle, WA 98195
United States

Anna Wald

University of Washington - Department of Medicine

Box 356340
1925 N.E. Pacific Street
Seattle, WA 98195-6340
United States

Division of Allergy and Infectious Diseases, University of Washington ( email )

David M. Koelle

Benaroya Research Institute at Virginia Mason ( email )

United States

William Kwok (Contact Author)

Benaroya Research Institute at Virginia Mason ( email )

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