Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals

By Alba Grifoni, D. Weiskopf, S. Ramirez, J. Mateus, J. Dan, C. Moderbacher, Stephen A. Rawlings, A. Sutherland, L. Premkumar, R. Jadi and 10 more. Cell, 2020

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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.

Subfields: Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/df331478ec23166904874baa5f42347b3ecc30ee

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Citations in the corpus

SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies (2021, neutral): “It should be noted that all plasma and sera tested completely inhibited entry at the lowest dilution tested and that T cell responses will contribute to control of SARS-CoV-2 infection, particularly in re-infected convalescent patients (Grifoni et al., 2020; Peng et al., 2020).”
COVID-19 and the human innate immune system (2021, background): “…and assuming that the majority of humankind does not have an extended cross-reaction to other viruses of the coronavirus family (Braun et al., 2020; Grifoni et al., 2020; Mateus et al., 2020), the introduction of SARS-CoV-2 into the human population is one of the biggest evolutionary events in the…”
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection (2021, methodology): “This could potentially underestimate CD8 T cell memory, as 15-mer peptides can be suboptimal for detection of some antigen-specific CD8 T cells (53); however, pools of predicted SARS-CoV2 class I epitope of optimal size also detected virus-specific CD8 T cells in ~70% of individuals 1 to 2 months PS”
Preexisting and de novo humoral immunity to SARS-CoV-2 in humans (2020, background): “Together with pre-existing T cell (12-14) and B cell memory (10, 15), antibody cross-reactivity between seasonal HCoVs and SARSCoV-2 may have important ramifications for natural infection.”
COVID-19 neutralizing antibodies predict disease severity and survival (2020, neutral): “The differences in humoral response induction may stem from a combination of factors, including host permissibility to viral replication and a rapid response from innate immune effector cells and cytotoxic T cells, some of which have been postulated to arise from cross-reactive memory cells to other”
Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications (2020, background): “Whereas immunoglobulin G (IgG) levels reportedly drop slightly ~8weeks after symptom onset (24, 25), recovered patients maintain high spike protein–specific IgG titers (6, 26).”
Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients (2021, background): “, 2020) and cellular components (Grifoni et al., 2020; Braun et al., 2020; Le Bert et al., 2020; Weiskopf et al., 2020) of adaptive immunity are induced in SARS-CoV-2-infected individuals, but their roles in viral control or disease pathogenesis need to be clarified.”