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| Status |
Public on Dec 20, 2022 |
| Title |
Single-cell transcriptomes and T Cell receptors of vaccine-expanded Apolipoprotein B-specific T cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Atherosclerotic cardiovascular diseases are the major cause of death worldwide. CD4 T cells responding to Apolipoprotein B (ApoB), the core protein of most lipoproteins, have been identified as critical disease modulators. In healthy individuals, ApoB-reactive (ApoB+) CD4 T cells are mostly regulatory T cells (Tregs), which exert anti-inflammatory effects. Yet, they may obtain pro-inflammatory features and thus become proatherogenic. Evidence from animal studies suggests that vaccination against certain major histocompatibility complex (MHC) II-binding ApoB peptides induces an expansion of ApoB+ Tregs and thus confers atheroprotection. To date, in-depth phenotyping of vaccine-expanded ApoB+ T cells has not yet been performed. To this end, we vaccinated C57BL/6J mice with the ApoB-peptide P6 (ApoB978-993 TGAYSNASSTESASY) and performed single-cell RNA sequencing of tetramer-sorted P6+ T cells. P6+ cells were clonally expanded (one major, two minor clones) and formed a transcriptional cluster distinct from clusters mainly containing non-expanded P6+ and P6- cells. Transcriptomic profiling revealed that most expanded P6+ cells had a strong Treg signature and highly expressed genes mediating suppressive function. Yet, some expanded P6+ cells only had a residual Treg signature and expressed genes related to T helper 1 (TH1) cells, which are proatherogenic. Modeling the T cell receptor (TCR) and P6:MHC‐II interaction showed that only 3 amino acid residues in each the α and β chain contact the P6 peptide in the MHC-II groove and thus determine the specificity of this TCR to P6. Our data begin to reveal the vaccination-induced response to an ApoB epitope.
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| Overall design |
Single-cell RNA sequencing of tetramer-sorted P6+ T cells
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| Contributor(s) |
Nettersheim FS, Ghosheh Y, Winkels H, Kobiyama K, Durant C, Armstrong Suthahar SS, Brunel S, Roy P, Dileepan T, Jenkins MK, Zajonc DM, Ley K |
| Citation(s) |
36684560 |
| Submission date |
Dec 19, 2022 |
| Last update date |
Feb 06, 2023 |
| Contact name |
Klaus Ley |
| E-mail(s) |
KLEY@augusta.edu
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| Organization name |
La Jolla Institute for Immunology
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| Lab |
Ley Lab
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| Street address |
9420 Athena Cir
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| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (176)
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| Relations |
| BioProject |
PRJNA913827 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE221281_Counts.csv.gz |
1.7 Mb |
(ftp)(http) |
CSV |
| GSE221281_Metadata.csv.gz |
2.2 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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