tetano
Editor, Senior Moderator
iScience
. 2023 Jun 16;26(6):106937.
doi: 10.1016/j.isci.2023.106937. Epub 2023 May 22. Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection
Martina Milighetti[SUP] 1 [/SUP], Yanchun Peng[SUP] 2 3 [/SUP], Cedric Tan[SUP] 4 [/SUP], Michal Mark[SUP] 5 [/SUP], Gayathri Nageswaran[SUP] 1 [/SUP], Suzanne Byrne[SUP] 1 [/SUP], Tahel Ronel[SUP] 1 [/SUP], Tom Peacock[SUP] 1 [/SUP], Andreas Mayer[SUP] 1 [/SUP], Aneesh Chandran[SUP] 1 [/SUP], Joshua Rosenheim[SUP] 1 [/SUP], Matthew Whelan[SUP] 1 [/SUP], Xuan Yao[SUP] 3 [/SUP], Guihai Liu[SUP] 3 [/SUP], Suet Ling Felce[SUP] 3 [/SUP], Tao Dong[SUP] 2 3 [/SUP], Alexander J Mentzer[SUP] 6 [/SUP], Julian C Knight[SUP] 3 6 [/SUP], Francois Balloux[SUP] 4 [/SUP], Erez Greenstein[SUP] 5 [/SUP], Shlomit Reich-Zeliger[SUP] 5 [/SUP], Corinna Pade[SUP] 7 [/SUP], Joseph M Gibbons[SUP] 7 [/SUP], Amanda Semper[SUP] 8 [/SUP], Tim Brooks[SUP] 8 [/SUP], Ashley Otter[SUP] 8 [/SUP], Daniel M Altmann[SUP] 9 [/SUP], Rosemary J Boyton[SUP] 10 11 [/SUP], Mala K Maini[SUP] 1 [/SUP], Aine McKnight[SUP] 7 [/SUP], Charlotte Manisty[SUP] 12 [/SUP], Thomas A Treibel[SUP] 12 [/SUP], James C Moon[SUP] 12 [/SUP]; COVIDsortium Investigators; Mahdad Noursadeghi[SUP] 1 [/SUP], Benny Chain[SUP] 1 [/SUP]
Affiliations
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.
. 2023 Jun 16;26(6):106937.
doi: 10.1016/j.isci.2023.106937. Epub 2023 May 22. Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection
Martina Milighetti[SUP] 1 [/SUP], Yanchun Peng[SUP] 2 3 [/SUP], Cedric Tan[SUP] 4 [/SUP], Michal Mark[SUP] 5 [/SUP], Gayathri Nageswaran[SUP] 1 [/SUP], Suzanne Byrne[SUP] 1 [/SUP], Tahel Ronel[SUP] 1 [/SUP], Tom Peacock[SUP] 1 [/SUP], Andreas Mayer[SUP] 1 [/SUP], Aneesh Chandran[SUP] 1 [/SUP], Joshua Rosenheim[SUP] 1 [/SUP], Matthew Whelan[SUP] 1 [/SUP], Xuan Yao[SUP] 3 [/SUP], Guihai Liu[SUP] 3 [/SUP], Suet Ling Felce[SUP] 3 [/SUP], Tao Dong[SUP] 2 3 [/SUP], Alexander J Mentzer[SUP] 6 [/SUP], Julian C Knight[SUP] 3 6 [/SUP], Francois Balloux[SUP] 4 [/SUP], Erez Greenstein[SUP] 5 [/SUP], Shlomit Reich-Zeliger[SUP] 5 [/SUP], Corinna Pade[SUP] 7 [/SUP], Joseph M Gibbons[SUP] 7 [/SUP], Amanda Semper[SUP] 8 [/SUP], Tim Brooks[SUP] 8 [/SUP], Ashley Otter[SUP] 8 [/SUP], Daniel M Altmann[SUP] 9 [/SUP], Rosemary J Boyton[SUP] 10 11 [/SUP], Mala K Maini[SUP] 1 [/SUP], Aine McKnight[SUP] 7 [/SUP], Charlotte Manisty[SUP] 12 [/SUP], Thomas A Treibel[SUP] 12 [/SUP], James C Moon[SUP] 12 [/SUP]; COVIDsortium Investigators; Mahdad Noursadeghi[SUP] 1 [/SUP], Benny Chain[SUP] 1 [/SUP]
Affiliations
- PMID: 37275518
- PMCID: PMC10201888
- DOI: 10.1016/j.isci.2023.106937
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.