SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells
Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 memory T cells is poorly understood. Here, we utilize DNA-barcoded MHC-multimers combined with scRNAseq and scTCRseq to capture the ex vivo profile of SARS-CoV-2-responsive T cells within a cohort of individuals with one, two, or three antigen exposures, including vaccination, primary infection, and breakthrough infection. We found that the order of exposure determined the relative distribution between spike- and non-spike-specific responses, with vaccination after infection leading to further expansion of spike-specific T cells and differentiation to a CCR7-CD45RA+ effector phenotype. In contrast, individuals experiencing a breakthrough infection mount vigorous non-spike-specific responses. In-depth analysis of over 4,000 epitope-specific T cell receptor sequences demonstrates that all types of exposures elicit diverse repertoires characterized by shared, dominant TCR motifs, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and that current vaccination protocols continue to expand and differentiate spike-specific memory responses.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2022 |
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| Enthalten in: |
medRxiv : the preprint server for health sciences - (2022) vom: 26. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Minervina, Anastasia A [VerfasserIn] |
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| Anmerkungen: |
Date Revised 05.11.2023 published: Electronic UpdateIn: Nat Immunol. 2022 Apr 5;:. - PMID 35383307 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2021.07.12.21260227 |
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| PPN (Katalog-ID): |
NLM328862967 |
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| 100 | 1 | |a Minervina, Anastasia A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells |
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| 500 | |a Date Revised 05.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: Nat Immunol. 2022 Apr 5;:. - PMID 35383307 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 memory T cells is poorly understood. Here, we utilize DNA-barcoded MHC-multimers combined with scRNAseq and scTCRseq to capture the ex vivo profile of SARS-CoV-2-responsive T cells within a cohort of individuals with one, two, or three antigen exposures, including vaccination, primary infection, and breakthrough infection. We found that the order of exposure determined the relative distribution between spike- and non-spike-specific responses, with vaccination after infection leading to further expansion of spike-specific T cells and differentiation to a CCR7-CD45RA+ effector phenotype. In contrast, individuals experiencing a breakthrough infection mount vigorous non-spike-specific responses. In-depth analysis of over 4,000 epitope-specific T cell receptor sequences demonstrates that all types of exposures elicit diverse repertoires characterized by shared, dominant TCR motifs, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and that current vaccination protocols continue to expand and differentiate spike-specific memory responses | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Pogorelyy, Mikhail V |e verfasserin |4 aut | |
| 700 | 1 | |a Kirk, Allison M |e verfasserin |4 aut | |
| 700 | 1 | |a Crawford, Jeremy Chase |e verfasserin |4 aut | |
| 700 | 1 | |a Allen, E Kaitlynn |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, Ching-Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Mettelman, Robert C |e verfasserin |4 aut | |
| 700 | 1 | |a Allison, Kim J |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Chun-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Brice, David C |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xun |e verfasserin |4 aut | |
| 700 | 1 | |a Vegesana, Kasi |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Trivedi, Sanchit |e verfasserin |4 aut | |
| 700 | 1 | |a Kottapalli, Pratibha |e verfasserin |4 aut | |
| 700 | 1 | |a Darnell, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a McNeely, Suzanne |e verfasserin |4 aut | |
| 700 | 1 | |a Olsen, Scott R |e verfasserin |4 aut | |
| 700 | 1 | |a Schultz-Cherry, Stacey |e verfasserin |4 aut | |
| 700 | 1 | |a Estepp, Jeremie H |e verfasserin |4 aut | |
| 700 | 0 | |a SJTRC Study Team |e verfasserin |4 aut | |
| 700 | 1 | |a McGargill, Maureen A |e verfasserin |4 aut | |
| 700 | 1 | |a Wolf, Joshua |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Paul G |e verfasserin |4 aut | |
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