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

Martina Milighetti; Yanchun Peng; Cedric Tan; Michal Mark; Gayathri Nageswaran; Suzanne Byrne; Tahel Ronel; Tom Peacock; Andreas Mayer; Aneesh Chandran; Joshua Rosenheim; Matthew Whelan; Xuan Yao; Guihai Liu; Suet Ling Felce; Tao Dong; Alexander J. Mentzer; Julian C. Knight; Francois Balloux; Erez Greenstein; Shlomit Reich-Zeliger; Corinna Pade; Joseph M. Gibbons; Amanda Semper; Tim Brooks; Ashley Otter; Daniel M. Altmann; Rosemary J. Boyton; Mala K. Maini; Aine McKnight; Charlotte Manisty; Thomas A. Treibel; James C. Moon; COVIDsortium Investigators; Mahdad Noursadeghi; Benny Chain

doi:10.1016/j.isci.2023.106937

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

Martina Milighetti, Yanchun Peng, Cedric Tan, Michal Mark, Gayathri Nageswaran, Suzanne Byrne, Tahel Ronel, Tom Peacock, Andreas Mayer, Aneesh Chandran, Joshua Rosenheim, Matthew Whelan, Xuan Yao, Guihai Liu, Suet Ling Felce, Tao Dong, Alexander J. Mentzer, Julian C. Knight, Francois Balloux, Erez GreensteinShlomit Reich-Zeliger, Corinna Pade, Joseph M. Gibbons, Amanda Semper, Tim Brooks, Ashley Otter, Daniel M. Altmann, Rosemary J. Boyton, Mala K. Maini, Aine McKnight, Charlotte Manisty, Thomas A. Treibel, James C. Moon, COVIDsortium Investigators, Mahdad Noursadeghi, Benny Chain

Norwich Medical School

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	106937
Journal	iScience
Volume	26
Issue number	6
Early online date	2 Jun 2023
DOIs	https://doi.org/10.1016/j.isci.2023.106937
Publication status	Published - 16 Jun 2023

Keywords

Biological sciences
Cell biology
Immunity
Immunology

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Milighetti, M., Peng, Y., Tan, C., Mark, M., Nageswaran, G., Byrne, S., Ronel, T., Peacock, T., Mayer, A., Chandran, A., Rosenheim, J., Whelan, M., Yao, X., Liu, G., Felce, S. L., Dong, T., Mentzer, A. J., Knight, J. C., Balloux, F., ... Chain, B. (2023). Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection. iScience, 26(6), Article 106937. https://doi.org/10.1016/j.isci.2023.106937

@article{472e85a0b50b48159690962043427f1e,

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

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.",

keywords = "Biological sciences, Cell biology, Immunity, Immunology",

author = "Martina Milighetti and Yanchun Peng and Cedric Tan and Michal Mark and Gayathri Nageswaran and Suzanne Byrne and Tahel Ronel and Tom Peacock and Andreas Mayer and Aneesh Chandran and Joshua Rosenheim and Matthew Whelan and Xuan Yao and Guihai Liu and Felce, {Suet Ling} and Tao Dong and Mentzer, {Alexander J.} and Knight, {Julian C.} and Francois Balloux and Erez Greenstein and Shlomit Reich-Zeliger and Corinna Pade and Gibbons, {Joseph M.} and Amanda Semper and Tim Brooks and Ashley Otter and Altmann, {Daniel M.} and Boyton, {Rosemary J.} and Maini, {Mala K.} and Aine McKnight and Charlotte Manisty and Treibel, {Thomas A.} and Moon, {James C.} and {COVIDsortium Investigators} and Mahdad Noursadeghi and Benny Chain and Hickling, {Lauren M.}",

note = "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.",

year = "2023",

month = jun,

day = "16",

doi = "10.1016/j.isci.2023.106937",

language = "English",

volume = "26",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier",

number = "6",

}

Milighetti, M, Peng, Y, Tan, C, Mark, M, Nageswaran, G, Byrne, S, Ronel, T, Peacock, T, Mayer, A, Chandran, A, Rosenheim, J, Whelan, M, Yao, X, Liu, G, Felce, SL, Dong, T, Mentzer, AJ, Knight, JC, Balloux, F, Greenstein, E, Reich-Zeliger, S, Pade, C, Gibbons, JM, Semper, A, Brooks, T, Otter, A, Altmann, DM, Boyton, RJ, Maini, MK, McKnight, A, Manisty, C, Treibel, TA, Moon, JC, COVIDsortium Investigators, Noursadeghi, M & Chain, B 2023, 'Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection', iScience, vol. 26, no. 6, 106937. https://doi.org/10.1016/j.isci.2023.106937

TY - JOUR

T1 - Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

AU - Milighetti, Martina

AU - Peng, Yanchun

AU - Tan, Cedric

AU - Mark, Michal

AU - Nageswaran, Gayathri

AU - Byrne, Suzanne

AU - Ronel, Tahel

AU - Peacock, Tom

AU - Mayer, Andreas

AU - Chandran, Aneesh

AU - Rosenheim, Joshua

AU - Whelan, Matthew

AU - Yao, Xuan

AU - Liu, Guihai

AU - Felce, Suet Ling

AU - Dong, Tao

AU - Mentzer, Alexander J.

AU - Knight, Julian C.

AU - Balloux, Francois

AU - Greenstein, Erez

AU - Reich-Zeliger, Shlomit

AU - Pade, Corinna

AU - Gibbons, Joseph M.

AU - Semper, Amanda

AU - Brooks, Tim

AU - Otter, Ashley

AU - Altmann, Daniel M.

AU - Boyton, Rosemary J.

AU - Maini, Mala K.

AU - McKnight, Aine

AU - Manisty, Charlotte

AU - Treibel, Thomas A.

AU - Moon, James C.

AU - COVIDsortium Investigators

AU - Noursadeghi, Mahdad

AU - Chain, Benny

AU - Hickling, Lauren M.

N1 - 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.

PY - 2023/6/16

Y1 - 2023/6/16

N2 - 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.

AB - 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.

KW - Biological sciences

KW - Cell biology

KW - Immunity

KW - Immunology

UR - http://www.scopus.com/inward/record.url?scp=85165650534&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2023.106937

DO - 10.1016/j.isci.2023.106937

M3 - Article

AN - SCOPUS:85165650534

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 6

M1 - 106937

ER -

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

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Keywords

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