An immunodominant NP105–113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease
Peng Y., Felce SL., Dong D., Penkava F., Mentzer AJ., Yao X., Liu G., Yin Z., Chen J-L., Lu Y., Wellington D., Wing PAC., Dominey-Foy DCC., Jin C., Wang W., Hamid MA., Fernandes RA., Wang B., Fries A., Zhuang X., Ashley N., Rostron T., Waugh C., Sopp P., Hublitz P., Beveridge R., Tan TK., Dold C., Kwok AJ., Rich-Griffin C., Dejnirattisa W., Liu C., Kurupati P., Nassiri I., Watson RA., Tong O., Taylor CA., Kumar Sharma P., Sun B., Curion F., Revale S., Garner LC., Jansen K., Ferreira RC., Attar M., Fry JW., Russell RA., Stauss HJ., James W., Townsend A., Ho L-P., Klenerman P., Mongkolsapaya J., Screaton GR., Dendrou C., Sansom SN., Bashford-Rogers R., Chain B., Smith GL., McKeating JA., Fairfax BP., Bowness P., McMichael AJ., Ogg G., Knight JC., Dong T.
AbstractNP105–113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105–113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105–113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105–113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105–113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.