Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

Milighetti, Martina, Peng, Yanchun, Tan, Cedric, Mark, Michal, Nageswaran, Gayathri, Byrne, Suzanne, Ronel, Tahel, Peacock, Tom, Mayer, Andreas, Chandran, Aneesh, Rosenheim, Joshua, Whelan, Matthew, Yao, Xuan, Liu, Guihai, Felce, Suet Ling, Dong, Tao, Mentzer, Alexander J., Knight, Julian C., Balloux, Francois, Greenstein, Erez, Reich-Zeliger, Shlomit, Pade, Corinna, Gibbons, Joseph M., Semper, Amanda, Brooks, Tim, Otter, Ashley, Altmann, Daniel M., Boyton, Rosemary J., Maini, Mala K., McKnight, Aine, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Noursadeghi, Mahdad and Chain, Benny and COVIDsortium Investigators (2023) Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection. iScience, 26 (6). ISSN 2589-0042

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Abstract

T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection.

Item Type:	Article
Additional Information:	Data and code availability: •The COVIDsortium TCR sequencing data have been deposited at NCBI Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra) and mouse TCR sequencing data have been deposited at Sequence Read Archive) and are publicly available under project accession number SRA:PRJNA718557. All other data are available in the main text or the supplemental information. •All code for analysis and generating individual figure panels are available on GitHub, and links to the repositories are provided in the key resources table. •Any additional information required to reanalyse the data reported in this paper is available from the lead contact upon request. Requests will be responded to within 4 weeks of receipt.
Uncontrolled Keywords:	biological sciences,cell biology,immunity,immunology
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	04 Mar 2025 14:30
Last Modified:	09 Mar 2025 07:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98656
DOI:	10.1016/j.isci.2023.106937

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