COVID-19 Patients Form Memory CD8+ T Cells that Recognize a Small Set of Shared Immunodominant Epitopes in SARS-CoV-2

Ferretti, Andrew P.; Kula, Tomasz; Wang, Yifan; Nguyen, Dalena M.V.; Weinheimer, Adam; Dunlap, Garrett S.; Xu, Qikai; Nabilsi, Nancy H.; Perullo, Candace R.; Cristofaro, Alexander; Whitton, Holly; Virbasius, Amy; Olivier, Kenneth J.; Buckner, Lyndsey R.; Alistar, Angela; Whitman, Eric D.; Bertino, Sarah A.; Chattopadhyay, Shrikanta; MacBeath, Gavin

doi:10.2139/ssrn.3669387

Cited by 16 publications

(17 citation statements)

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“…(13) Interestingly, the peptide reactivity that had the strongest correlation with ADCC derives from an intra-virion portion of CoV2 M (residues 169-224) which is a known T cell epitope. (18) For structural context, we mapped the dominant CoV2 S regions onto the mature folded S protein structure ( Figure 2B). (19) SARS-CoV-2 and endemic coronavirus cross-reactivity Many immunodominant CoV2 peptides are homologous to HCoV peptides, and HCoV peptides were more frequently recognized by the CCP compared to Pre-COVID plasma.…”

Section: Resultsmentioning

confidence: 99%

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

Morgenlander

Henson

Monaco

et al. 2021

Journal of Clinical Investigation

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COVID-19 convalescent plasma, particularly plasma with high-titer SARS-CoV-2 (CoV2) antibodies, is one of the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the four endemic human coronavirus (HCoV) genomes in 126 COVID-19 convalescent plasma donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies to SARS-CoV-2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a two-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting therapeutic plasma with desired functionalities.

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Section: Resultsmentioning

confidence: 99%

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

Morgenlander

Henson

Monaco

et al. 2021

Journal of Clinical Investigation

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“…Because SARS-CoV N protein exhibits more than 90% homology of amino acid sequence to that of SARS-CoV-2 (Grifoni et al, 2020a), it is natural to suspect that T cell responses to the N protein of SARS-CoV-2 may also provide cellular immune protection, which may last for a long time. Recently, using predicted or established peptide libraries of the S and N proteins, a number of SARS-CoV-2 T cell epitopes were identified in COVID-19 convalescent patients across independent studies, providing important clues for vaccine development (Chour et al, 2020; Ferretti et al, 2020; Le Bert et al, 2020b; Nelde et al, 2020; Peng et al, 2020; Poran et al, 2020; Shomuradova et al, 2020; Snyder et al, 2020). However, detailed information of how SARS-CoV-2 induces cellular immune responses is currently limited.…”

Section: Introductionmentioning

confidence: 99%

Identification of Cross-Reactive CD8⁺T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants

Shen

Han

et al. 2020

Preprint

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Despite the growing knowledge of T cell responses and their epitopes in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins, N361-369 (KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369 mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369 epitope could be processed and endogenously presented to elicit the activation and cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.

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“…Additional recent studies have decoded blood T cell clonotypes and recognized antigen epitopes restricted by HLA class I or II in mostly convalescent COVID-19 patients and controls (19,32,38,40,67,69,70). Taken together, the studies show that anti-SARS-CoV-2 T cell responses target immunodominant epitopes broadly spread across the viral proteome mostly beyond the S protein, involve convergent and shared T cell clonotypes among patients and persist for several months post-recovery.…”

Section: A Need For Decoding Reactivities Phenotypes and Recognizedmentioning

confidence: 84%

“…Taken together, the studies show that anti-SARS-CoV-2 T cell responses target immunodominant epitopes broadly spread across the viral proteome mostly beyond the S protein, involve convergent and shared T cell clonotypes among patients and persist for several months post-recovery. Epitope localization outside regions with high mutational variation could suggest that T cell vaccine responses may not be prone to virus escape (69). An increased diversity but not intensity of SARS-CoV-2 T cell responses is associated with recovery from mild vs. severe disease (40).…”

Section: A Need For Decoding Reactivities Phenotypes and Recognizedmentioning

confidence: 99%

An Effective COVID-19 Vaccine Needs to Engage T Cells

Sauer¹,

Harris²

2020

Front. Immunol.

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COVID-19 Patients Form Memory CD8+ T Cells that Recognize a Small Set of Shared Immunodominant Epitopes in SARS-CoV-2

Cited by 16 publications

References 0 publications

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

Identification of Cross-Reactive CD8⁺T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants

An Effective COVID-19 Vaccine Needs to Engage T Cells

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COVID-19 Patients Form Memory CD8+ T Cells that Recognize a Small Set of Shared Immunodominant Epitopes in SARS-CoV-2

Cited by 16 publications

References 0 publications

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

Identification of Cross-Reactive CD8+T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants

An Effective COVID-19 Vaccine Needs to Engage T Cells

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Product

Resources

About

Identification of Cross-Reactive CD8⁺T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants