tetano
Editor, Senior Moderator
Nat Immunol
. 2022 Mar 21.
doi: 10.1038/s41590-022-01175-5. Online ahead of print.
Establishment and recall of SARS-CoV-2 spike epitope-specific CD4 [SUP]+[/SUP] T cell memory
Kathleen M Wragg[SUP] #[/SUP][SUP] 1 [/SUP], Wen Shi Lee[SUP] #[/SUP][SUP] 1 [/SUP], Marios Koutsakos[SUP] #[/SUP][SUP] 1 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Thakshila Amarasena[SUP] 1 [/SUP], Arnold Reynaldi[SUP] 2 [/SUP], Grace Gare[SUP] 1 [/SUP], Penny Konstandopoulos[SUP] 1 [/SUP], Kirsty R Field[SUP] 1 [/SUP], Robyn Esterbauer[SUP] 1 [/SUP], Helen E Kent[SUP] 1 [/SUP], Miles P Davenport[SUP] 2 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Stephen J Kent[SUP] 3 4 [/SUP], Jennifer A Juno[SUP] 5 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit CD4[SUP]+[/SUP] T cell responses to the spike protein, including circulating follicular helper T (cT[SUB]FH[/SUB]) cells that correlate with neutralizing antibodies. Using a novel HLA-DRB1*15:01/S[SUB]751[/SUB] tetramer to track spike-specific CD4[SUP]+[/SUP] T cells, we show that primary infection or vaccination induces robust S[SUB]751[/SUB]-specific CXCR5[SUP]-[/SUP] and cT[SUB]FH[/SUB] cell memory responses. Secondary exposure induced recall of CD4[SUP]+[/SUP] T cells with a transitory CXCR3[SUP]+[/SUP] phenotype, and drove expansion of cT[SUB]FH[/SUB] 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[SUP]-[/SUP] and cT[SUB]FH[/SUB] populations. Following a third vaccine dose, the rapid re-expansion of spike-specific CD4[SUP]+[/SUP] T cells contrasted with the comparatively delayed increase in antibody titers. Overall, we demonstrate that stable pools of cT[SUB]FH[/SUB] and memory CD4[SUP]+[/SUP] 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.
. 2022 Mar 21.
doi: 10.1038/s41590-022-01175-5. Online ahead of print.
Establishment and recall of SARS-CoV-2 spike epitope-specific CD4 [SUP]+[/SUP] T cell memory
Kathleen M Wragg[SUP] #[/SUP][SUP] 1 [/SUP], Wen Shi Lee[SUP] #[/SUP][SUP] 1 [/SUP], Marios Koutsakos[SUP] #[/SUP][SUP] 1 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Thakshila Amarasena[SUP] 1 [/SUP], Arnold Reynaldi[SUP] 2 [/SUP], Grace Gare[SUP] 1 [/SUP], Penny Konstandopoulos[SUP] 1 [/SUP], Kirsty R Field[SUP] 1 [/SUP], Robyn Esterbauer[SUP] 1 [/SUP], Helen E Kent[SUP] 1 [/SUP], Miles P Davenport[SUP] 2 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Stephen J Kent[SUP] 3 4 [/SUP], Jennifer A Juno[SUP] 5 [/SUP]
Affiliations
- PMID: 35314848
- DOI: 10.1038/s41590-022-01175-5
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit CD4[SUP]+[/SUP] T cell responses to the spike protein, including circulating follicular helper T (cT[SUB]FH[/SUB]) cells that correlate with neutralizing antibodies. Using a novel HLA-DRB1*15:01/S[SUB]751[/SUB] tetramer to track spike-specific CD4[SUP]+[/SUP] T cells, we show that primary infection or vaccination induces robust S[SUB]751[/SUB]-specific CXCR5[SUP]-[/SUP] and cT[SUB]FH[/SUB] cell memory responses. Secondary exposure induced recall of CD4[SUP]+[/SUP] T cells with a transitory CXCR3[SUP]+[/SUP] phenotype, and drove expansion of cT[SUB]FH[/SUB] 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[SUP]-[/SUP] and cT[SUB]FH[/SUB] populations. Following a third vaccine dose, the rapid re-expansion of spike-specific CD4[SUP]+[/SUP] T cells contrasted with the comparatively delayed increase in antibody titers. Overall, we demonstrate that stable pools of cT[SUB]FH[/SUB] and memory CD4[SUP]+[/SUP] 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.