Frontiers in Immunology (Jan 2025)

Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels

  • Thomas M. Snyder,
  • Rachel M. Gittelman,
  • Mark Klinger,
  • Damon H. May,
  • Edward J. Osborne,
  • Ruth Taniguchi,
  • H. Jabran Zahid,
  • Ian M. Kaplan,
  • Jennifer N. Dines,
  • Matthew T. Noakes,
  • Ravi Pandya,
  • Xiaoyu Chen,
  • Summer Elasady,
  • Emily Svejnoha,
  • Peter Ebert,
  • Mitchell W. Pesesky,
  • Patricia De Almeida,
  • Hope O’Donnell,
  • Quinn DeGottardi,
  • Gladys Keitany,
  • Jennifer Lu,
  • Allen Vong,
  • Rebecca Elyanow,
  • Paul Fields,
  • Hussein Al-Asadi,
  • Julia Greissl,
  • Lance Baldo,
  • Simona Semprini,
  • Claudio Cerchione,
  • Fabio Nicolini,
  • Massimiliano Mazza,
  • Ottavia M. Delmonte,
  • Kerry Dobbs,
  • Rocio Laguna-Goya,
  • Gonzalo Carreño-Tarragona,
  • Santiago Barrio,
  • Luisa Imberti,
  • Alessandra Sottini,
  • Eugenia Quiros-Roldan,
  • Camillo Rossi,
  • Andrea Biondi,
  • Laura Rachele Bettini,
  • Mariella D’Angio,
  • Paolo Bonfanti,
  • Miranda F. Tompkins,
  • Camille Alba,
  • Clifton Dalgard,
  • Vittorio Sambri,
  • Giovanni Martinelli,
  • Jason D. Goldman,
  • Jason D. Goldman,
  • James R. Heath,
  • Helen C. Su,
  • Luigi D. Notarangelo,
  • Estela Paz-Artal,
  • Joaquin Martinez-Lopez,
  • Bryan Howie,
  • Jonathan M. Carlson,
  • Harlan S. Robins

DOI
https://doi.org/10.3389/fimmu.2024.1488860
Journal volume & issue
Vol. 15

Abstract

Read online

IntroductionT cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.MethodsHere, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared “public” T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.ResultsCollectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3–7 = 85.1% [95% CI = 79.9–89.7]; Day 8–14 = 94.8% [90.7–98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1–98.3]).DiscussionThe approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.

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