Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1299-1315.e4 |
| Journal | Immunity |
| Volume | 55 |
| Issue number | 7 |
| DOIs | |
| State | Published - 12 Jul 2022 |
Keywords
- B cells
- CD4 T cells
- CD8 T cells
- COVID-19
- SARS-CoV-2
- children
- memory T cells
- tetramer-specific
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In: Immunity, Vol. 55, No. 7, 12.07.2022, p. 1299-1315.e4.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - SARS-CoV-2-specific T cell memory with common TCRαβ motifs is established in unvaccinated children who seroconvert after infection
AU - Rowntree, Louise C.
AU - Nguyen, Thi H.O.
AU - Kedzierski, Lukasz
AU - Neeland, Melanie R.
AU - Petersen, Jan
AU - Crawford, Jeremy Chase
AU - Allen, Lilith F.
AU - Clemens, E. Bridie
AU - Chua, Brendon
AU - McQuilten, Hayley A.
AU - Minervina, Anastasia A.
AU - Pogorelyy, Mikhail V.
AU - Chaurasia, Priyanka
AU - Tan, Hyon Xhi
AU - Wheatley, Adam K.
AU - Jia, Xiaoxiao
AU - Amanat, Fatima
AU - Krammer, Florian
AU - Allen, E. Kaitlynn
AU - Sonda, Sabrina
AU - Flanagan, Katie L.
AU - Jumarang, Jaycee
AU - Pannaraj, Pia S.
AU - Licciardi, Paul V.
AU - Kent, Stephen J.
AU - Bond, Katherine A.
AU - Williamson, Deborah A.
AU - Rossjohn, Jamie
AU - Thomas, Paul G.
AU - Tosif, Shidan
AU - Crawford, Nigel W.
AU - van de Sandt, Carolien E.
AU - Kedzierska, Katherine
N1 - Funding Information: SARS-CoV-2 serological assays (US Provisional Application #62/994252, 63/018457, 63/020503, and 63/024436) and NDV-based SARS-CoV-2 vaccines (US Provisional Application #63/251020) list F.K. as a co-inventor. F.A. is also a co-inventor of the serological assay patents. Patent applications were submitted by the Icahn School of Medicine at Mount Sinai. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Third Rock Ventures, Seqirus, and Avimex. F.K. laboratory collaborates with Pfizer on the animal models of SARS-CoV-2. P.G.T. is on the SAB of Immunoscape and Cytoagents, has consulted for JNJ, received travel support and/or honoraria from Illumina, 10X Genomics, and has patents on TCR discovery and expression. P.S.P. received research grants from Astra Zeneca and Pfizer and has served on advisory boards for Sanofi Pasteur and Seqirus. Funding Information: We thank the participating families involved in the study and Kate Dohle, Jill Nguyen, Isabella Overmars, Philip Sutton, and Daniel Pellicci for their support with the cohorts. We thank the Melbourne Cytometry Platform for the technical assistance. This work was supported by the NHMRC Leadership Investigator Grant to K.K. ( 1173871 ); the NHMRC Emerging Leadership Level 1 Investigator Grant to T.H.O.N. (# 1194036 ) and A.K.W. (# 1173433 ); the Research Grants Council of the Hong Kong Special Administrative Region, China (# T11-712/19-N ) to K.K.; the Doherty Collaborative Seed grant to M.R.N., A.K.W., S.J.K., S.T., C.E.v.d.S., and K.K.; the Victorian Government (S.J.K. and A.K.W.); the Clifford Craig Foundation Project Grant to K.L.F. and K.K. (#186); the MRFF award (# 2002073 ) to S.J.K. and A.K.W.; the MRFF Award (# 1202445 ) to K.K.; the MRFF Award (# 2005544 ) to K.K., S.J.K., and A.K.W.; the NHMRC program grant 1149990 (S.J.K.); the NHMRC project grant 1162760 (A.K.W.); the NIH contract CIVC-HRP ( HHS-NIH-NIAID-BAA2018 ) to P.G.T. and K.K.; and the NIAID UO1 grant 1U01AI144616-01 “Dissection of Influenza Vaccination and Infection for Childhood Immunity” (DIVINCI) to F.K., P.G.T., K.K., and P.S.P. S.J.K. is supported by the NHMRC Senior Principal Research Fellowship (# 1136322 ). C.E.v.d.S. received funding from the European Union’s Horizon 2020 research program under the Marie Skłodowska-Curie grant agreement (# 792532 ) and is supported by the ARC-DECRA Fellowship (# DE200100185 ) and University of Melbourne Establishment grant. J.R. is supported by an ARC Laureate Fellowship. J.C.C. and P.G.T. are supported by the NIH NIAID R01 AI136514-03 and the ALSAC at St. Jude. P.V.L. is supported by an NHMRC Career Development Fellowship. Work in the F.K. laboratory was partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, #HHSN272201400008C), the Centers of Excellence for Influenza Research and Response (CEIRR, #75N93021C00014), by the Collaborative Influenza Vaccine Innovation Centers (CIVICs, #75N93019C00051), and by institutional funds. We acknowledge the RCH Foundation for their support of the study and recruitment of the families involved. Recruitment of the household contacts was enable by COVID-19 Grant, Department of Jobs, Precincts and Regions, Victoria State Government and Research Grant, DHB Foundation, Australia. The graphical abstract was created with BioRender.com . Funding Information: We thank the participating families involved in the study and Kate Dohle, Jill Nguyen, Isabella Overmars, Philip Sutton, and Daniel Pellicci for their support with the cohorts. We thank the Melbourne Cytometry Platform for the technical assistance. This work was supported by the NHMRC Leadership Investigator Grant to K.K. (1173871); the NHMRC Emerging Leadership Level 1 Investigator Grant to T.H.O.N. (#1194036) and A.K.W. (#1173433); the Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N) to K.K.; the Doherty Collaborative Seed grant to M.R.N. A.K.W. S.J.K. S.T. C.E.v.d.S. and K.K.; the Victorian Government (S.J.K. and A.K.W.); the Clifford Craig Foundation Project Grant to K.L.F. and K.K. (#186); the MRFF award (#2002073) to S.J.K. and A.K.W.; the MRFF Award (#1202445) to K.K.; the MRFF Award (#2005544) to K.K. S.J.K. and A.K.W.; the NHMRC program grant 1149990 (S.J.K.); the NHMRC project grant 1162760 (A.K.W.); the NIH contract CIVC-HRP (HHS-NIH-NIAID-BAA2018) to P.G.T. and K.K.; and the NIAID UO1 grant 1U01AI144616-01 “Dissection of Influenza Vaccination and Infection for Childhood Immunity” (DIVINCI) to F.K. P.G.T. K.K. and P.S.P. S.J.K. is supported by the NHMRC Senior Principal Research Fellowship (#1136322). C.E.v.d.S. received funding from the European Union's Horizon 2020 research program under the Marie Skłodowska-Curie grant agreement (#792532) and is supported by the ARC-DECRA Fellowship (#DE200100185) and University of Melbourne Establishment grant. J.R. is supported by an ARC Laureate Fellowship. J.C.C. and P.G.T. are supported by the NIH NIAID R01 AI136514-03 and the ALSAC at St. Jude. P.V.L. is supported by an NHMRC Career Development Fellowship. Work in the F.K. laboratory was partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, #HHSN272201400008C), the Centers of Excellence for Influenza Research and Response (CEIRR, #75N93021C00014), by the Collaborative Influenza Vaccine Innovation Centers (CIVICs, #75N93019C00051), and by institutional funds. We acknowledge the RCH Foundation for their support of the study and recruitment of the families involved. Recruitment of the household contacts was enable by COVID-19 Grant, Department of Jobs, Precincts and Regions, Victoria State Government and Research Grant, DHB Foundation, Australia. The graphical abstract was created with BioRender.com. K.K. led the study. K.K. and C.E.v.d.S. supervised the study. L.C.R. T.H.O.N. L.K. C.E.v.d.S. and K.K. designed the experiments. L.C.R. T.H.O.N. L.K. L.F.A. E.B.C. X.J. and H.-X.T. performed and analyzed the experiments. E.B.C. and H.A.M. analyzed the data. J.P. A.A.M. M.V.P. P.C. A.K.W. F.A. F.K. S.J.K. and J.R. provided the crucial reagents. M.R.N. E.K.A. S.S. K.L.F. J.J. P.S.P. P.V.L. K.A.B. D.A.W. P.G.T. S.T. and N.W.C. recruited the patient cohorts. L.C.R. T.H.O.N. J.C.C. L.F.A. H.A.M. P.G.T. and C.E.v.d.S. analyzed the TCR sequences. L.C.R. T.H.O.N. L.K. P.G.T. S.T. C.E.v.d.S. and K.K. provided the intellectual input into the study design and data interpretation. L.C.R. T.H.O.N. C.E.v.d.S. and K.K. wrote the manuscript. All authors reviewed and approved the manuscript. SARS-CoV-2 serological assays (US Provisional Application #62/994252, 63/018457, 63/020503, and 63/024436) and NDV-based SARS-CoV-2 vaccines (US Provisional Application #63/251020) list F.K. as a co-inventor. F.A. is also a co-inventor of the serological assay patents. Patent applications were submitted by the Icahn School of Medicine at Mount Sinai. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Third Rock Ventures, Seqirus, and Avimex. F.K. laboratory collaborates with Pfizer on the animal models of SARS-CoV-2. P.G.T. is on the SAB of Immunoscape and Cytoagents, has consulted for JNJ, received travel support and/or honoraria from Illumina, 10X Genomics, and has patents on TCR discovery and expression. P.S.P. received research grants from Astra Zeneca and Pfizer and has served on advisory boards for Sanofi Pasteur and Seqirus. Publisher Copyright: © 2022 The Author(s)
PY - 2022/7/12
Y1 - 2022/7/12
N2 - 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.
AB - 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.
KW - B cells
KW - CD4 T cells
KW - CD8 T cells
KW - COVID-19
KW - SARS-CoV-2
KW - children
KW - memory T cells
KW - tetramer-specific
UR - http://www.scopus.com/inward/record.url?scp=85133245714&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2022.06.003
DO - 10.1016/j.immuni.2022.06.003
M3 - Article
C2 - 35750048
AN - SCOPUS:85133245714
SN - 1074-7613
VL - 55
SP - 1299-1315.e4
JO - Immunity
JF - Immunity
IS - 7
ER -