Dissecting the heterogeneity of DENV vaccine-elicited cellular immunity using single-cell RNA sequencing and metabolic profiling

Autor: Benjamin Gabriel, Kaitlin Victor, Jeffrey R. Currier, Wiriya Rutvisuttinunt, Adam T. Waickman, Richard G. Jarman, Tao Li, Carey L. Medin, Kristin Hatch, Heather Friberg
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cellular immunity
Live attenuated vaccines
T cell
Science
Receptors
Antigen
T-Cell
General Physics and Astronomy
Dengue Vaccines
02 engineering and technology
Computational biology
Dengue virus
Biology
CD8-Positive T-Lymphocytes
medicine.disease_cause
Vaccines
Attenuated
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Immunogenicity
Vaccine
Single-cell analysis
Immunity
medicine
Humans
Transcriptomics
lcsh:Science
Immunity
Cellular
Multidisciplinary
Sequence Analysis
RNA
Gene Expression Profiling
T-cell receptor
General Chemistry
021001 nanoscience & nanotechnology
3. Good health
Gene expression profiling
030104 developmental biology
medicine.anatomical_structure
Metabolome
lcsh:Q
Single-Cell Analysis
0210 nano-technology
Transcriptome
Immunologic Memory
CD8
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019)
Nature Communications
ISSN: 2041-1723
DOI: 10.1038/s41467-019-11634-7
Popis: Generating effective and durable T cell immunity is a critical prerequisite for vaccination against dengue virus (DENV) and other viral diseases. However, understanding the molecular mechanisms of vaccine-elicited T cell immunity remains a critical knowledge gap in vaccinology. In this study, we utilize single-cell RNA sequencing (scRNAseq) and longitudinal TCR clonotype analysis to identify a unique transcriptional signature present in acutely activated and clonally-expanded T cells that become committed to the memory repertoire. This effector/memory-associated transcriptional signature is dominated by a robust metabolic transcriptional program. Based on this transcriptional signature, we are able to define a set of markers that identify the most durable vaccine-reactive memory-precursor CD8+ T cells. This study illustrates the power of scRNAseq as an analytical tool to assess the molecular mechanisms of host control and vaccine modality in determining the magnitude, diversity and persistence of vaccine-elicited cell-mediated immunity.
Using a combination of single-cell RNA sequencing and TCR clonotype analysis on longitudinal samples from dengue vaccinated individuals, Waickman et al. here define a transcriptional signature in acutely-activated T cells that is associated with durable CD8+ T cell memory.
Databáze: OpenAIRE
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