Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection.
Martina Milighetti; Yanchun Peng; Cedric C.S. Tan; Michal Mark; Gayathri Nageswaran; Suzanne Byrne; Tahel Ronel; Thomas Peacock; Andreas Mayer; Aneesh Chandran; Joshua Rosenheim; Matthew Wheelan; Xuan Yao; Guihai Liu; Suet Ling Felce; Tao Dong; Alexander J Mentzer; Julian Charles 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.
Preprint
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| PREPRINT-BIORXIV | ID: ppbiorxiv-515436
We analyzed the dynamics of the earliest T cell response to SARS-COV-2. A wave of TCRs strongly but transiently expand during infection, 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. Most epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains, but not with circulating human coronaviruses. Many expanding CDR3s were also present at high precursor frequency in pre-pandemic TCR repertoires. A similar set of early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the pre-infection naive repertoire. High frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection. One-Sentence SummaryHigh frequency naive precursors underly the rapid T cell response during the crucial early phases of acute viral infection.
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