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Deconvoluting the T Cell Response to SARS-CoV-2: Specificity Versus Chance and Cognate Cross-Reactivity.

Abstract
SARS-CoV-2 infection takes a mild or clinically inapparent course in the majority of humans who contract this virus. After such individuals have cleared the virus, only the detection of SARS-CoV-2-specific immunological memory can reveal the exposure, and hopefully the establishment of immune protection. With most viral infections, the presence of specific serum antibodies has provided a reliable biomarker for the exposure to the virus of interest. SARS-CoV-2 infection, however, does not reliably induce a durable antibody response, especially in sub-clinically infected individuals. Consequently, it is plausible for a recently infected individual to yield a false negative result within only a few months after exposure. Immunodiagnostic attention has therefore shifted to studies of specific T cell memory to SARS-CoV-2. Most reports published so far agree that a T cell response is engaged during SARS-CoV-2 infection, but they also state that in 20-81% of SARS-CoV-2-unexposed individuals, T cells respond to SARS-CoV-2 antigens (mega peptide pools), allegedly due to T cell cross-reactivity with Common Cold coronaviruses (CCC), or other antigens. Here we show that, by introducing irrelevant mega peptide pools as negative controls to account for chance cross-reactivity, and by establishing the antigen dose-response characteristic of the T cells, one can clearly discern between cognate T cell memory induced by SARS-CoV-2 infection vs. cross-reactive T cell responses in individuals who have not been infected with SARS-CoV-2.
AuthorsAlexander A Lehmann, Greg A Kirchenbaum, Ting Zhang, Pedro A Reche, Paul V Lehmann
JournalFrontiers in immunology (Front Immunol) Vol. 12 Pg. 635942 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
PMID34127926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 Lehmann, Kirchenbaum, Zhang, Reche and Lehmann.
Chemical References
  • Antigens, Viral
  • Biomarkers
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Peptides
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
Topics
  • Antigens, Viral (immunology)
  • Biomarkers
  • COVID-19 (immunology, metabolism, virology)
  • Cross Reactions (immunology)
  • Cytokines (metabolism)
  • Epitopes, T-Lymphocyte (immunology)
  • Host-Pathogen Interactions (immunology)
  • Humans
  • Immunodominant Epitopes (immunology)
  • Immunologic Memory
  • Peptides (immunology)
  • Protein Binding
  • SARS-CoV-2 (immunology)
  • Spike Glycoprotein, Coronavirus (immunology)
  • T-Lymphocytes (immunology, metabolism)

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