@article{33e3716dce0e47f5801ddf5f5e3aa815,
title = "SARS-CoV-2-specific T cell memory with common TCRαβ motifs is established in unvaccinated children who seroconvert after infection",
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.",
keywords = "CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, COVID-19, Epitopes, T-Lymphocyte, Humans, Immunologic Memory, Receptors, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta/genetics, SARS-CoV-2, Spike Glycoprotein, Coronavirus",
author = "Rowntree, \{Louise C\} and Nguyen, \{Thi H O\} and Lukasz Kedzierski and Neeland, \{Melanie R\} and Jan Petersen and Crawford, \{Jeremy Chase\} and Allen, \{Lilith F\} and Clemens, \{E Bridie\} and Brendon Chua and McQuilten, \{Hayley A\} and Minervina, \{Anastasia A\} and Pogorelyy, \{Mikhail V\} and Priyanka Chaurasia and Hyon-Xhi Tan and Wheatley, \{Adam K\} and Xiaoxiao Jia and Fatima Amanat and Florian Krammer and Allen, \{E Kaitlynn\} and Sabrina Sonda and Flanagan, \{Katie L\} and Jaycee Jumarang and Pannaraj, \{Pia S\} and Licciardi, \{Paul V\} and Kent, \{Stephen J\} and Bond, \{Katherine A\} and Williamson, \{Deborah A\} and Jamie Rossjohn and Thomas, \{Paul G\} and Shidan Tosif and Crawford, \{Nigel W\} and \{van de Sandt\}, \{Carolien E\} and Katherine Kedzierska",
note = "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{\textquoteright}s Horizon 2020 research program under the Marie Sk{\l}odowska-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.",
year = "2022",
month = jul,
day = "12",
doi = "10.1016/j.immuni.2022.06.003",
language = "English",
volume = "55",
pages = "1299--1315.e4",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "7",
}
SDG 3 Good Health and Well-being