Establishment and recall of SARS-CoV-2 spike epitope-specific CD4+ T cell memory

Kathleen M. Wragg, Wen Shi Lee, Marios Koutsakos, Hyon-Xhi Tan, Thakshila Amarasena, Arnold Reynaldi, Grace Gare, Penny Konstandopoulos, Kirsty R. Field, Robyn Esterbauer, Helen E. Kent, Miles P. Davenport, Adam K. Wheatley, Stephen J. Kent, Jennifer A. Juno

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31 Citations (Scopus)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit CD4+ T cell responses to the spike protein, including circulating follicular helper T (cTFH) cells that correlate with neutralizing antibodies. Using a novel HLA-DRB1*15:01/S751 tetramer to track spike-specific CD4+ T cells, we show that primary infection or vaccination induces robust S751-specific CXCR5 and cTFH cell memory responses. Secondary exposure induced recall of CD4+ T cells with a transitory CXCR3+ phenotype, and drove expansion of cTFH cells transiently expressing ICOS, CD38 and PD-1. In both contexts, cells exhibited a restricted T cell antigen receptor repertoire, including a highly public clonotype and considerable clonotypic overlap between CXCR5 and cTFH populations. Following a third vaccine dose, the rapid re-expansion of spike-specific CD4+ T cells contrasted with the comparatively delayed increase in antibody titers. Overall, we demonstrate that stable pools of cTFH and memory CD4+ T cells established by infection and/or vaccination are efficiently recalled upon antigen reexposure and may contribute to long-term protection against SARS-CoV-2.

Original languageEnglish
Pages (from-to)768-780
Number of pages13
JournalNature Immunology
Volume23
Issue number5
DOIs
Publication statusPublished - May 2022

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