An immunodominant NP105\u2013113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease

Yanchun Peng,Julian C Knight,Tiong Kit Tan,Timothy Rostron,Ricardo C Ferreira,Ricardo A Fernandes,William James,Graham Ogg,Piyush Kumar Sharma,Ryan Beveridge,Kathrin Jansen,Craig Waugh,Frank Penkava,Chang Liu,Ji‐Li Chen ,Prathiba Kurupati,Chen Jin,Robert Watson ,Juthathip Mongkolsapaya,Santiago Revale,Christina Dold,Bo Sun,Ling-Pei Ho,Orion Tong,Benjamin P Fairfax,Yongxu Lu,Rachael Bashford-Rogers,Danning Dong,Anastasia Fries,Megat Abd Hamid,Suet Ling Felce,Paul Klenerman,Charlotte Rich-Griffin,Xuan Yao,Dannielle Wellington,Wenbo Wang,Moustafa Attar,P Sopp ,Delaney Dominey-Foy ,Peter Ac Wing ,Alexander J Mentzer,Calliope A Dendrou ,Paul Bowness,Beibei Wang,Geoffrey L Smith,Benjamin M Chain ,Lucy C Garner,Chelsea Taylor ,Xiaodong Zhuang,Fabiola Curion,Alain Townsend,Hans J Stauss,Jeremy Fry ,Andrew Kwok ,Gavin Screaton ,Zixi Yin,Neil Ashley,Andrew J Mcmichael,Wanwisa Dejnirattisa,Stephen N Sansom,Michael D Moore ,Guihai Liu,Jane A Mckeating,Isar Nassiri,Philip Hublitz,Tao Dong

doi:10.1038/s41590-021-01084-z

Abstract

NP105–113-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.

Highlights

CD8+ T cells play a well-documented role in clearing viral infections
We found high similarity and convergence of T cell receptor (TCR) in human leukocyte antigen (HLA)-B*07:02-positive healthy and recovered individuals, with naive precursors identified in prepandemic samples supporting previous reports[7,10]
It is interesting that the immune memory pools postinfection (6 months convalescence) are narrowed but remain proportional; we found no bias toward high or low functional avidity TCRs during immune memory contraction

Summary

Introduction

CD8+ T cells play a well-documented role in clearing viral infections. Immunodominance is a central feature of CD8+ T cell responses in viral infections and understanding the nature of this response for a given infection, where they are shown to be protective, will be critical for the design of vaccines aiming to elicit optimal CD8+ T cell responses[1,2]. We saw stronger overall T cell responses in individuals recovered from severe COVID, which may be explained by high exposure to viral protein; we found an immunodominant epitope response (HLA-B*07:02 NP105–113-specific CD8+) which significantly associated with mild cases.

Results

Conclusion