Longitudinal analysis of T cell receptor repertoires reveals shared patterns of antigen-specific response to SARS-CoV-2 infection

Gittelman, Rachel M.; Lavezzo, Enrico; Snyder, Thomas M.; Zahid, H Jabran; Carty, Cara L.; Elyanow, Rebecca; Dalai, Sudeb C.; Kirsch, Ilan R.; Baldo, Lance; Manuto, Laura; Franchin, Elisa; Vecchio, Claudia Del; Pacenti, Monia; Boldrin, Caterina; Cattai, Margherita; Saluzzo, Francesca; Padoan, Andrea; Plebani, Mario; Simeoni, Fabio; Bordini, Jessica; Lorè, Nicola Ivan; Lazarević, Dejan; Cirillo, Daniela María; Ghia, Paolo; Toppo, Stefano; Carlson, Jonathan M.; Robins, Harlan; Crisanti, Andrea; Tonon, Giovanni

doi:10.1172/jci.insight.151849

Cited by 31 publications

(31 citation statements)

References 64 publications

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“…The immunoSEQ assay is a high throughput ultra-deep sequence-based method to quantify spike-specific T-cell responses after natural infection or vaccination [17] . This method allowed us to assess the breadth and depth of the spike-specific TCR repertoire for all vaccinees at baseline and after the first and second vaccination.…”

Section: Bnt162b2 Vaccination Expands the Spike-specific T-cell Responsementioning

confidence: 99%

Durable immune responses after BNT162b2 vaccination in home-dwelling old adults

et al. 2023

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Section: Bnt162b2 Vaccination Expands the Spike-specific T-cell Responsementioning

confidence: 99%

Durable immune responses after BNT162b2 vaccination in home-dwelling old adults

et al. 2023

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“…lungs and intestines) and subsequently re-enter the blood via the lymphatic system to potentially enhance immune surveillance ( Walsh et al, 2011 ; Kruger et al, 2008 ). While TCR-β sequencing is an effective technique to characterize the SARS-CoV-2 T-cell repertoire it does not capture functional information, therefore future studies should determine the functional status of these exercise responsive clones ( Gittelman et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Exercise mobilizes diverse antigen specific T-cells and elevates neutralizing antibodies in humans with natural immunity to SARS CoV-2

Baker¹,

Zúñiga²,

Smith³

et al. 2023

Brain, Behavior, & Immunity - Health

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“…4). To more generally study the heterogeneity and longitudinal dynamics of SARS-CoV-2 reactive CD4 + T cells, we counted the breadth of clones in each sample exactly matching a set of CD4 +associated TRB sequences that were previously found to be enriched in SARS-CoV-2 convalescent versus healthy control repertoires 34 (diagnostic breadth). These TRB sequences, derived using the ImmunoSEQ assay (Adaptive Biotechnologies) [35][36][37] , were previously assigned to S (n = 917) or non-Spike (n = 1564) SARS-CoV-2 antigens 38 (see Methods).…”

Section: Hybrid Immunity Elicits Highly Public S-speci C Tcr Motifsmentioning

confidence: 99%

CD8+ T cell clonotypes from prior SARS-CoV-2 infection predominate during the cellular immune response to mRNA vaccination

Ford¹,

Mayer-Blackwell²,

Jing³

et al. 2022

Preprint

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Almost three years into the SARS-CoV-2 pandemic, hybrid immunity is highly prevalent worldwide and more protective than vaccination or prior infection alone. Given emerging resistance of variant strains to neutralizing antibodies (nAb), it is likely that T cells contribute to this protection. To understand how sequential SARS-CoV-2 infection and mRNA-vectored SARS-CoV-2 spike (S) vaccines affect T cell clonotype-level expansion kinetics, we identified and cross-referenced TCR sequences from thousands of S-reactive single cells against deeply sequenced peripheral blood TCR repertoires longitudinally collected from persons during COVID-19 convalescence through booster vaccination. Successive vaccinations recalled memory T cells and elicited antigen-specific T cell clonotypes not detected after infection. Vaccine-related recruitment of novel clonotypes and the expansion of S-specific clones were most strongly observed for CD8+ T cells. Severe COVID-19 illness was associated with a more diverse CD4+ T cell response to SARS-CoV-2 both prior to and after mRNA vaccination, suggesting imprinting of CD4+ T cells by severe infection. TCR sequence similarity search algorithms revealed myriad public TCR clusters correlating with human leukocyte antigen (HLA) alleles. Selected TCRs from distinct clusters functionally recognized S in the predicted HLA context, with fine viral peptide requirements differing between TCRs. Most subjects tested had S-specific T cells in the nasal mucosa after a 3rd mRNA vaccine dose. The blood and nasal T cell responses to vaccination revealed by clonal tracking were more heterogeneous than nAb boosts. Analysis of bulk and single cell TCR sequences reveals T cell kinetics and diversity at the clonotype level, without requiring prior knowledge of T cell epitopes or HLA restriction, providing a roadmap for rapid assessment of T cell responses to emerging pathogens.

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Longitudinal analysis of T cell receptor repertoires reveals shared patterns of antigen-specific response to SARS-CoV-2 infection

Cited by 31 publications

References 64 publications

Durable immune responses after BNT162b2 vaccination in home-dwelling old adults

Durable immune responses after BNT162b2 vaccination in home-dwelling old adults

Exercise mobilizes diverse antigen specific T-cells and elevates neutralizing antibodies in humans with natural immunity to SARS CoV-2

CD8+ T cell clonotypes from prior SARS-CoV-2 infection predominate during the cellular immune response to mRNA vaccination

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