ArticleImmunology and cell biology2016
Linking the T cell receptor to the single cell transcriptome in antigen-specific human T cells.
Article in Immunology and cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed.
- T cell immunomonitoring: a comparative analysis of traditional and novel methods to quantify and characterize human antigen-specific T cells.Nature protocols · 2026Review
- The T Cell Receptor: Molecular Sensor, Therapeutic Mediator and Probabilistic Driver of Adaptive Immunity.Immunological reviews · 2026Review
- Proportion, Function, and Generation of Dual Receptor Lymphocytes.Journal of immunology research · 2026Review
- Identification of Sjögren's disease-associated T cell receptor motifs through deep sequencing.JCI insight · 2025Article
- Umbilical cord blood-derived cytotoxic T lymphocytes target melanoma via HLA-A2-restricted tumour antigens.Clinical and translational medicine · 2025Article
- Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Single-Cell Multiomics Reveals TCR Clonotype-Specific Phenotype and Stemness Heterogeneity of T-ALL Cells.Cell proliferation · 2025Article
- Demonstration of T-Cell Monotypia Using Anti-TCRbeta1/2 (Diagnostics (Basel, Switzerland) · 2024Article
- Unified cross-modality integration and analysis of T cell receptors and T cell transcriptomes by low-resource-aware representation learning.Cell genomics · 2024Article
- Historical perspective and future directions: computational science in immuno-oncology.Journal for immunotherapy of cancer · 2024Review
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
- CARNature communications · 2023Article
- Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.Nature immunology · 2023Article
- T Cell Clonal Analysis Using Single-cell RNA Sequencing and Reference Maps.Bio-protocol · 2023Article
- Dual TCR-Expressing T Cells in Cancer: How Single-Cell Technologies Enable New Investigation.ImmunoHorizons · 2023Article
- Identification of human progenitors of exhausted CD8Nature communications · 2022Article
- Tumor microenvironment: barrier or opportunity towards effective cancer therapy.Journal of biomedical science · 2022Review
- Single-cell approaches to dissect adaptive immune responses involved in autoimmunity: the case of celiac disease.Mucosal immunology · 2022Review
- AIRR Community Guide to Planning and Performing AIRR-Seq Experiments.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Expansion of Unique Hepatitis C Virus-Specific Public CD8Journal of immunology (Baltimore, Md. : 1950) · 2021Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterogeneity of T cells is a hallmark of a successful adaptive immune response, harnessing the vast diversity of antigen-specific T cells into a coordinated evolution of effector and memory outcomes. The T cell receptor (TCR) repertoire is highly diverse to account for the highly heterogeneous antigenic world. During the response to a virus multiple individual clones of antigen specific CD8+ (Ag-specific) T cells can be identified against a single epitope and multiple epitopes are recognised. Advances in single-cell technologies have provided the potential to study Ag-specific T cell heterogeneity at both surface phenotype and transcriptome levels, thereby allowing investigation of the diversity within the same apparent sub-population. We propose a new method (VDJPuzzle) to reconstruct the native TCRαβ from single cell RNA-seq data of Ag-specific T cells and then to link these with the gene expression profile of individual cells. We applied this method using rare Ag-specific T cells isolated from peripheral blood of a subject who cleared hepatitis C virus infection. We successfully reconstructed productive TCRαβ in 56 of a total of 63 cells (89%), with double α and double β in 18, and 7% respectively, and double TCRαβ in 2 cells. The method was validated via standard single cell PCR sequencing of the TCR. We demonstrate that single-cell transcriptome analysis can successfully distinguish Ag-specific T cell populations sorted directly from resting memory cells in peripheral blood and sorted after ex vivo stimulation. This approach allows a detailed analysis of the TCR diversity and its relationship with the transcriptional profile of different clones.
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