SARS-CoV-2-specific T cell memory with common TCRαβ motifs is established in unvaccinated children who seroconvert after infection

As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination...

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Bibliographic Details
Published in:Immunity 2022-07, Vol.55 (7), p.1299-1315.e4
Main Authors: Rowntree, Louise C., Nguyen, Thi H.O., Kedzierski, Lukasz, Neeland, Melanie R., Petersen, Jan, Crawford, Jeremy Chase, Allen, Lilith F., Clemens, E. Bridie, Chua, Brendon, McQuilten, Hayley A., Minervina, Anastasia A., Pogorelyy, Mikhail V., Chaurasia, Priyanka, Tan, Hyon-Xhi, Wheatley, Adam K., Jia, Xiaoxiao, Amanat, Fatima, Krammer, Florian, Allen, E. Kaitlynn, Sonda, Sabrina, Flanagan, Katie L., Jumarang, Jaycee, Pannaraj, Pia S., Licciardi, Paul V., Kent, Stephen J., Bond, Katherine A., Williamson, Deborah A., Rossjohn, Jamie, Thomas, Paul G., Tosif, Shidan, Crawford, Nigel W., van de Sandt, Carolien E., Kedzierska, Katherine
Format: Article
Language:English
Subjects:
B cells
CD4+ T cells
CD4-Positive T-Lymphocytes
CD8+ T cells
CD8-Positive T-Lymphocytes
children
COVID-19
Epitopes, T-Lymphocyte
Humans
Immunologic Memory
memory T cells
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell, alpha-beta - genetics
SARS-CoV-2
Spike Glycoprotein, Coronavirus
tetramer-specific
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Summary:As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination. We analyzed epitope-specific T cells directly ex vivo using seven HLA class I and class II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable Spike-specific but lower ORF1a- and N-specific memory T cell responses compared with adults. This agreed with our TCR sequencing data showing reduced clonal expansion in children. A strong stem cell memory phenotype and common T cell receptor motifs were detected within tetramer-specific T cells in seroconverted children. Conversely, children who did not seroconvert had tetramer-specific T cells of predominantly naive phenotypes and diverse TCRαβ repertoires. Our study demonstrates the generation of SARS-CoV-2-specific T cell memory with common TCRαβ motifs in unvaccinated seroconverted children after their first virus encounter. [Display omitted] •SARS-CoV-2-specific T cells detected ex vivo in unvaccinated seroconverted children•Comparable Spike-T cell memory responses but lower ORF1a/N-responses found in children•Reduced clonal expansions within tetramer+ T cells seen in children compared with adults•Prevalent Tscm phenotype and TCR motif occur in SARS-CoV-2-specific T cells in children Children are at lower risk of developing severe COVID-19, yet their primary and memory immune responses are understudied. Rowntree et al. define ex vivo CD8+ and CD4+ T cell responses toward SARS-CoV-2 using peptide-HLA tetramers. They find that children have comparable Spike-specific but lower ORF1a- and N-specific memory T cell magnitude with less clonal expansion in comparison with adults.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2022.06.003