Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection.
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 None., Noursadeghi M., Chain B.
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.