PerspectiveCORONAVIRUS

SARS-CoV-2 T cell immunity: Specificity, function, durability, and role in protection

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Science Immunology  17 Jul 2020:
Vol. 5, Issue 49, eabd6160
DOI: 10.1126/sciimmunol.abd6160

Figures

  • Fig. 1 Hypothetical interactions between SARS-CoV-2–infected cells, antigen-presenting cells, and CD4 and CD8 T cells.

    Viral peptides (shown in dark green) will be processed from all parts of the SARS-CoV-2 proteome and presented to the TCR repertoire in the grooves of HLA I molecules on the infected cell and by HLA II molecules of antigen-presenting cells that have taken up debris from infected cells. SARS-CoV-2–reactive CD4 cells appear to be largely TH1-like, secreting IFN-γ, TNF-α, and IL-2. CD8 cells can secrete a similar cytokine profile but also lyse infected target cells. We are unaware of data at present clearly indicating a role of CD4 or CD8 T cells in lung immunopathology, but illustrate here the hypothetical likelihood of this.

Tables

  • Table 1 Summary of published studies analyzing T cell responses to SARS-CoV-2.

    AIM, activation-induced marker; ARDS, acute respiratory distress syndrome; HC, healthy control; ICS, intracellular cytokine staining; nd, not done; M, membrane antigen; N, nucleocapsid antigen; S, spike antigen; Tcm, central memory T cells; PBMC, peripheral blood mononuclear cell; NSP, non-structural protein; CTLA-4, cytotoxic T lymphocyte–associated protein 4; RBD, receptor binding domain.

    ManuscriptMethodsCohortT cell subsets
    and features
    Antigen
    hierarchy
    Epitope dataCytokine
    /effector
    function
    Cross-reactivity
    evidence
    Braun et al. (14)Spike peptide
    panel; AIM
    Mild, severe, ICU
    COVID-19
    CD38+HLA-DR+
    activated T cells
    Analysis limited
    to spike
    ndndYes: A third of HC
    responded to
    C-terminal
    peptides from
    spike.
    Thieme et al. (18)Peptide panels;
    ICS
    Moderate,
    severe, ICU
    COVID-19
    • CD4 response
    detected in 95%
    M > S > NndCD4 response:
    IFN-γ, IL-2,
    TNF-α; higher
    frequency of
    polyfunctional
    cells in patients
    with greater
    severity
    nd
    • CD8 response
    in 77%
    Sekine et al. (3)Peptide panels;
    ICS; AIM,
    tetramers
    Moderate to
    severe
    COVID-19;
    exposed family
    members
    • CD4:
    CD38+CD69+
    Ki67+ PD-1+
    M > NSeveral
    predicted HLA-A
    and HLA-B
    predicted
    binders from
    the full
    proteome used
    to make
    tetramers
    CD4 response:
    IFN-γ, IL-2,
    TNF-α;
    TH1-skewed
    response
    Yes: cross-reactive
    recognition of
    spike and M
    • CD8: CD38+
    CD39+ CD69+
    CTLA-4+
    HLA-DR+ Ki67+
    LAG 3+ TIM-3+
    “activated-
    cycling”
    phenotype
    CD8 response:
    IFN-γ, TNF-α,
    CD107a
    Peng et al. (7)Peptide pools
    (not ORF1); ICS;
    ELISpot;
    pentamers; T
    cell lines
    Recovered from
    mild to severe
    COVID-19
    Higher
    magnitude and
    broader breadth
    of T cell
    responses in
    severe cases in
    comparison with
    mild cases
    S > M > ORF3aSpike: 18
    peptides
    IFN-γ, IL-2, and
    TNF-α
    polyfunctional
    response in both
    CD4 and CD8,
    mild, and severe
    cases
    No: none
    observed in n = 16
    N: 10 peptides
    M: 6 peptides
    ORF3a: 4
    peptides
    ORF7a: 3
    peptides
    Grifoni et al. (8)Mega-pools;
    AIM; ICS
    Mild to severe
    COVID-19 and
    pre-2019
    samples
    Patients were
    convalescent
    and showed no
    evidence of
    lymphopenia.
    S > M > NAntigen
    mega-pools not
    resolved to the
    level of
    individual
    epitopes
    CD4 response
    mainly IFN-γ;
    CD8 is IFN-γ,
    TNF-α, and
    granzyme B
    Half of HC showed
    cross-reactivity
    with RBD from
    HCoV OC43 or
    NL63.
    Le Bert et al. (15)Peptide pools
    from N, ORF3
    NSP-7, and
    NSP-13
    Mild to severe
    COVID-19
    convalescent
    Response in
    100% to N
    epitopes
    Study focus on
    N
    N: 7 peptidesndAll patients with
    SARS-CoV showed
    cross-reactive
    response to
    SARS-CoV-2
    NP. Half of HC
    show cross-
    reactivity with
    epitopes in ORF-1
    NSP-7 and NSP-13.
    Gallais et al. (4)Peptide pools;
    ELISpot
    Household
    contacts of 7
    PCR+ cases
    Response in
    100% of index
    cases and in
    seronegative
    contacts
    S = M = N
    co-dominant
    ndndnd
    Weiskopf et al. (12)Mega-pools;
    AIM
    ICU ARDS
    including fatal
    cases
    • T cell
    lymphopenia
    S > “remainder of
    proteome mega-
    pool”
    Antigen
    mega-pools not
    resolved to the
    level of
    individual
    epitopes
    T cell culture
    supernatants
    contained: IFN-γ,
    TNF-α, IL-2, IL-5,
    IL-13, IL-10, IL-9,
    IL-17A, IL-17F,
    and IL-22
    Cross-reactivity in
    2 of 10 HC
    • Most responder
    cells were Tcm
    based on
    CD45RA and
    CCR7 expression.
    Oja et al. (2)Peptide pools;
    AIM; ICS; used
    PBMC and BAL
    Mild, severe, ICU
    COVID-19
    • T cell
    lymphopenia
    S > N > M > ORF3a.
    Spike response
    seen in
    BAL. Reduced
    response to
    spike and N in
    ICU cases
    ndMainly IFN-γ and
    TNF-α. IFN-γ
    response
    significantly
    lower in ICU
    cases
    No cross-reactivity
    found to spike
    peptides from
    S299E, S-OC43
    • PD-1 highest in
    most severe

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