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Review
. 2022 Oct 11;55(10):1764-1778.
doi: 10.1016/j.immuni.2022.08.008. Epub 2022 Aug 18.

SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic

Antonio Bertoletti  1 , Nina Le Bert  2 , Anthony T Tan  2
Affiliations
Review

SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic

Antonio Bertoletti et al. Immunity. .

Abstract

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increasing ability to evade neutralizing antibodies have emerged. Thus, earlier interest in defining the correlates of protection from infection, mainly mediated by humoral immunity, has shifted to correlates of protection from disease, which require a more comprehensive analysis of both humoral and cellular immunity. In this review, we summarized the evidence that supports the role of SARS-CoV-2-specific T cells induced by infection, by vaccination or by their combination (defined as hybrid immunity) in disease protection. We then analyzed the different epidemiological and virological variables that can modify the magnitude, function, and anatomical localization of SARS-CoV-2-specific T cells and their influence in the possible ability of T cells to protect the host from severe COVID-19 development.

Keywords: COVID-19 vaccines; hybrid immunity; immundominance; tissue-resident T cells.

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Conflict of interest statement

Declaration of interests A. Bertoletti, N. Le Bert and A.T. Tan reported a patent for a method to monitor SARS-CoV-2-specific T cells in biological samples pending and are the co-founders of T Cell Diagnostic (TCD), Ltd.

Figures

Figure 1
Figure 1
Localization, specificity, and composition of SARS-CoV-2-specific T cells in vaccinated, infected, and individuals with hybrid immunity This illustration summarizes the key features of SARS-CoV-2-specific T cell responses observed in individuals who were vaccinated, infected, or developed hybrid immunity after breakthrough infection post-vaccination. The anatomical niche(s) occupied by the SARS-CoV-2 T cells (localization), the viral antigen(s) targeted by the indicated T cells (specificity), and the CD8+ and CD4+ T cell subsets induced in each scenario (composition) were described.
Figure 2
Figure 2
The determinants of disease-protecting SARS-CoV-2-specific T cell responses This illustration summarizes the six proposed determinants of antigen-specific T cell responses that can mediate protection against COVID-19 disease. Magnitude refers to the quantitative measurement of sampled total SARS-CoV-2-specific T cells derived from flow cytometry or ELIspot assays. Specificity refers to the T cell recognition of various structural or non-structural protein targets, particularly their derived epitopes, that are presented by MHC molecules. Of consequent interest are the antigenic breadth and associated hierarchies of disease protection or immunodominance. Cross-reactivity refers to the ability of a T cell, primed by other antigens, to recognize MHC-presented SARS-CoV-2-derived epitopes. Antigenic history, likely to related coronaviruses, could shape an individual’s protective responses to SARS-CoV-2 encounter. Composition refers to the T cell subsets (i.e., CD4+ and CD8+) and their associated niches and cytokines produced during antigen encounter or infection. Kinetics of viral antigen production is a virological property referring to the succession of translation of SARS-CoV-2 mRNA during infection, which could influence T cell-mediated protection against disease. Localization refers to the anatomic niche(s) occupied by protective SARS-CoV-2-specific T cells.
See this image and copyright information in PMC

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