SARS-CoV-2 epitope-specific CD4+ memory T cell responses across COVID-19 disease severity and antibody durability

Sci Immunol. 2022 Jul 22;7(73):eabl9464. doi: 10.1126/sciimmunol.abl9464. Epub 2022 Jul 22.

Abstract

CD4+ T cells are central to long-term immunity against viruses through the functions of T helper 1 (TH1) and T follicular helper (TFH) cell subsets. To better understand the role of these subsets in coronavirus disease 2019 (COVID-19) immunity, we conducted a longitudinal study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ T cell and antibody responses in convalescent individuals who seroconverted during the first wave of the pandemic in Boston, MA, USA, across a range of COVID-19 disease severities. Analyses of spike (S) and nucleocapsid (N) epitope-specific CD4+ T cells using peptide and major histocompatibility complex class II (pMHCII) tetramers demonstrated expanded populations of T cells recognizing the different SARS-CoV-2 epitopes in most individuals compared with prepandemic controls. Individuals who experienced a milder disease course not requiring hospitalization had a greater percentage of circulating TFH (cTFH) and TH1 cells among SARS-CoV-2-specific cells. Analysis of SARS-CoV-2-specific CD4+ T cells responses in a subset of individuals with sustained anti-S antibody responses after viral clearance also revealed an increased proportion of memory cTFH cells. Our findings indicate that efficient early disease control also predicts favorable long-term adaptive immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4-Positive T-Lymphocytes
  • COVID-19*
  • Epitopes
  • Humans
  • Longitudinal Studies
  • Memory T Cells
  • SARS-CoV-2*
  • Severity of Illness Index

Substances

  • Epitopes