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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 has prompted booster immunizations. However, repeated antigen exposure effects on SARS-CoV-2 memory T cells are poorly understood. Here, we utilize MHC-multimers with scRNAseq to profile SARS-CoV-2-responsive T ce...

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Autores principales: Minervina, Anastasia A., Pogorelyy, Mikhail V., Kirk, Allison M., Crawford, Jeremy Chase, Allen, E. Kaitlynn, Chou, Ching-Heng, Mettelman, Robert C., Allison, Kim J., Lin, Chun-Yang, Brice, David C., Zhu, Xun, Vegesana, Kasi, Wu, Gang, Trivedi, Sanchit, Kottapalli, Pratibha, Darnell, Daniel, McNeely, Suzanne, Olsen, Scott R., Schultz-Cherry, Stacey, Estepp, Jeremie H., McGargill, Maureen A., Wolf, Joshua, Thomas, Paul G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106845/
https://www.ncbi.nlm.nih.gov/pubmed/35383307
http://dx.doi.org/10.1038/s41590-022-01184-4
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author Minervina, Anastasia A.
Pogorelyy, Mikhail V.
Kirk, Allison M.
Crawford, Jeremy Chase
Allen, E. Kaitlynn
Chou, Ching-Heng
Mettelman, Robert C.
Allison, Kim J.
Lin, Chun-Yang
Brice, David C.
Zhu, Xun
Vegesana, Kasi
Wu, Gang
Trivedi, Sanchit
Kottapalli, Pratibha
Darnell, Daniel
McNeely, Suzanne
Olsen, Scott R.
Schultz-Cherry, Stacey
Estepp, Jeremie H.
McGargill, Maureen A.
Wolf, Joshua
Thomas, Paul G.
author_facet Minervina, Anastasia A.
Pogorelyy, Mikhail V.
Kirk, Allison M.
Crawford, Jeremy Chase
Allen, E. Kaitlynn
Chou, Ching-Heng
Mettelman, Robert C.
Allison, Kim J.
Lin, Chun-Yang
Brice, David C.
Zhu, Xun
Vegesana, Kasi
Wu, Gang
Trivedi, Sanchit
Kottapalli, Pratibha
Darnell, Daniel
McNeely, Suzanne
Olsen, Scott R.
Schultz-Cherry, Stacey
Estepp, Jeremie H.
McGargill, Maureen A.
Wolf, Joshua
Thomas, Paul G.
author_sort Minervina, Anastasia A.
collection PubMed
description Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence has prompted booster immunizations. However, repeated antigen exposure effects on SARS-CoV-2 memory T cells are poorly understood. Here, we utilize MHC-multimers with scRNAseq to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two, or three antigen exposures, including vaccination, primary, and breakthrough infection. Exposure order determined the distribution between spike- and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7-CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell receptor sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.
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spelling pubmed-91068452022-10-05 SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells Minervina, Anastasia A. Pogorelyy, Mikhail V. Kirk, Allison M. Crawford, Jeremy Chase Allen, E. Kaitlynn Chou, Ching-Heng Mettelman, Robert C. Allison, Kim J. Lin, Chun-Yang Brice, David C. Zhu, Xun Vegesana, Kasi Wu, Gang Trivedi, Sanchit Kottapalli, Pratibha Darnell, Daniel McNeely, Suzanne Olsen, Scott R. Schultz-Cherry, Stacey Estepp, Jeremie H. McGargill, Maureen A. Wolf, Joshua Thomas, Paul G. Nat Immunol Article Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence has prompted booster immunizations. However, repeated antigen exposure effects on SARS-CoV-2 memory T cells are poorly understood. Here, we utilize MHC-multimers with scRNAseq to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two, or three antigen exposures, including vaccination, primary, and breakthrough infection. Exposure order determined the distribution between spike- and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7-CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell receptor sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory. 2022-05 2022-04-05 /pmc/articles/PMC9106845/ /pubmed/35383307 http://dx.doi.org/10.1038/s41590-022-01184-4 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Minervina, Anastasia A.
Pogorelyy, Mikhail V.
Kirk, Allison M.
Crawford, Jeremy Chase
Allen, E. Kaitlynn
Chou, Ching-Heng
Mettelman, Robert C.
Allison, Kim J.
Lin, Chun-Yang
Brice, David C.
Zhu, Xun
Vegesana, Kasi
Wu, Gang
Trivedi, Sanchit
Kottapalli, Pratibha
Darnell, Daniel
McNeely, Suzanne
Olsen, Scott R.
Schultz-Cherry, Stacey
Estepp, Jeremie H.
McGargill, Maureen A.
Wolf, Joshua
Thomas, Paul G.
SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells
title SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells
title_full SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells
title_fullStr SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells
title_full_unstemmed SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells
title_short SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells
title_sort sars-cov-2 antigen exposure history shapes phenotypes and specificity of memory cd8 t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106845/
https://www.ncbi.nlm.nih.gov/pubmed/35383307
http://dx.doi.org/10.1038/s41590-022-01184-4
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