PMID- 36263073
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231020
DP  - 2022 Oct 10
TI  - CD8(+) T cell clonotypes from prior SARS-CoV-2 infection predominate during the 
      cellular immune response to mRNA vaccination.
LID - rs.3.rs-2146712 [pii]
LID - 10.21203/rs.3.rs-2146712/v1 [doi]
AB  - 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.
FAU - Ford, Emily S
AU  - Ford ES
FAU - Mayer-Blackwell, Koshlan
AU  - Mayer-Blackwell K
FAU - Jing, Lichen
AU  - Jing L
FAU - Sholukh, Anton M
AU  - Sholukh AM
FAU - St Germain, Russell
AU  - St Germain R
FAU - Bossard, Emily L
AU  - Bossard EL
FAU - Xie, Hong
AU  - Xie H
FAU - Pulliam, Thomas H
AU  - Pulliam TH
FAU - Jani, Saumya
AU  - Jani S
FAU - Selke, Stacy
AU  - Selke S
FAU - Burrow, Carlissa J
AU  - Burrow CJ
FAU - McClurkan, Christopher L
AU  - McClurkan CL
FAU - Wald, Anna
AU  - Wald A
FAU - Holbrook, Michael R
AU  - Holbrook MR
FAU - Eaton, Brett
AU  - Eaton B
FAU - Eudy, Elizabeth
AU  - Eudy E
FAU - Murphy, Michael
AU  - Murphy M
FAU - Postnikova, Elena
AU  - Postnikova E
FAU - Robins, Harlan S
AU  - Robins HS
FAU - Elyanow, Rebecca
AU  - Elyanow R
FAU - Gittelman, Rachel M
AU  - Gittelman RM
FAU - Ecsedi, Matyas
AU  - Ecsedi M
FAU - Wilcox, Elise
AU  - Wilcox E
FAU - Chapuis, Aude G
AU  - Chapuis AG
FAU - Fiore-Gartland, Andrew
AU  - Fiore-Gartland A
FAU - Koelle, David M
AU  - Koelle DM
LA  - eng
GR  - K08 AI148588/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20221010
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
PMC - PMC9580387
OTO - NOTNLM
OT  - SARS-CoV-2
OT  - T cell receptor
OT  - clustering analysis
OT  - immune repertoire
OT  - mRNA vaccine
COIS- Competing Interest Declaration HSR and RE are employees of Adaptive 
      Biotechnologies, Inc. Other authors: no competing interest.
EDAT- 2022/10/21 06:00
MHDA- 2022/10/21 06:01
PMCR- 2022/10/19
CRDT- 2022/10/20 02:54
PHST- 2022/10/21 06:00 [pubmed]
PHST- 2022/10/21 06:01 [medline]
PHST- 2022/10/20 02:54 [entrez]
PHST- 2022/10/19 00:00 [pmc-release]
AID - rs.3.rs-2146712 [pii]
AID - 10.21203/rs.3.rs-2146712/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2022 Oct 10:rs.3.rs-2146712. doi: 10.21203/rs.3.rs-2146712/v1.