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

KM Wragg; WS Lee; M Koutsakos; HX Tan; T Amarasena; A Reynaldi; G Gare; P Konstandopoulos; KR Field; R Esterbauer; HE Kent; MP Davenport; AK Wheatley; SJ Kent; JA Juno

Journal article

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

KM Wragg, WS Lee, M Koutsakos, HX Tan, T Amarasena, A Reynaldi, G Gare, P Konstandopoulos, KR Field, R Esterbauer, HE Kent, MP Davenport, AK Wheatley, SJ Kent, JA Juno

Nature Immunology | Published : 2022

DOI: 10.1038/s41590-022-01175-5

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 p..

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University of Melbourne Researchers

Kathleen Wragg Author

Wen Shi Lee Author

Marios Koutsakos Author

Hyon Xhi Tan Author

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

The authors thank the study participants for their involvement and provision of samples. We thank V. Jameson at the Melbourne Cytometry Platform (Melbourne Brain Centre node) for the provision of cell sorting services, and C. Batten for technical assistance. This work was funded by a National Health and Medical Research Council (NHMRC) Ideas Grant to J.A.J. (GNT2004398), NHMRC program grant to S.J.K. and M.P.D. (1149990), a Medical Research Future Fund grant to J.A.J., A.K.W. and S.J.K. (GNT2005544) and the Victorian Government. M.K., M.P.D., A.K.W., S.J.K. and J.A.J. are funded by NHMRC Investigator grants (1195698, 1173027, 1173433, 1136322 and 2009308, respectively). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.