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.
journal_name
Immunol Cell Bioljournal_title
Immunology and cell biologyauthors
Eltahla AA,Rizzetto S,Pirozyan MR,Betz-Stablein BD,Venturi V,Kedzierska K,Lloyd AR,Bull RA,Luciani Fdoi
10.1038/icb.2016.16subject
Has Abstractpub_date
2016-07-01 00:00:00pages
604-11issue
6eissn
0818-9641issn
1440-1711pii
icb201616journal_volume
94pub_type
杂志文章abstract::T-cell repertoire is selected according to self peptide-MHC (major histocompatibility complex) complexes in the thymus. Although most peripheral T cells recognize specific pathogen-derived peptides complexed to self-MHC exclusively, some possess cross-reactivity to other self or foreign peptides presented by self-MHC ...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2014.113
更新日期:2015-05-01 00:00:00
abstract::Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) accumulation, tau pathology and neuroinflammation. Recently, there has been considerable interest in the role of neuroinflammation in directly contributing to the progression of AD. Studies in mice and humans have identified a role for microglial cells, th...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1111/imcb.12301
更新日期:2020-01-01 00:00:00
abstract::Pseudomonas aeruginosa ocular infection causes extensive corneal neovascularization. The purpose of the present study was to investigate the role of the angiogenic factors macrophage inflammatory protein-2 (MIP-2) and vascular endothelial growth factor (VEGF) in the regulation of corneal neovascularization during P. a...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.1440-1711.2002.01094.x
更新日期:2002-08-01 00:00:00
abstract::Interferon regulatory factor (IRF) family members impart cell-type specificity to toll-like receptor (TLR) signalling, and we recently identified a role for IRF6 in TLR2 signalling in epithelial cells. TLR3 has a well-characterized role in wound healing in the skin, and here, we examined TLR3-dependent IRF6 functions ...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2015.77
更新日期:2015-10-01 00:00:00
abstract::CD45 (lymphocyte common antigen) is a receptor-linked protein tyrosine phosphatase that is expressed on all leucocytes, and which plays a crucial role in the function of these cells. On T cells the extracellular domain of CD45 is expressed in several different isoforms, and the particular isoform(s) expressed depends ...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.1997.68
更新日期:1997-10-01 00:00:00
abstract::The recognition of T cell receptors (TCR) by purified major histocompatibility complex (MHC) class II-peptide complexes in the absence of costimulatory signals leads to the induction of T cell non-responsiveness or anergy. In a recent study using human T cell clones, it was observed that prolonged incubation of restin...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1996.13
更新日期:1996-02-01 00:00:00
abstract::Mice infected with Sarcocystis muris showed a significant reduction in plaque-forming cells (PFC) and delayed-type hypersensitivity (DHS) responses to an unrelated protein antigen, bovine gamma-globulin, when compared with uninfected controls. This immunosuppression was observed only when infection preceded immunizati...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1988.26
更新日期:1988-01-01 00:00:00
abstract::The cellular effects of biodiesel emissions particulate matter (BDEP) and petroleum diesel emissions particulate matter (PDEP) were compared using a human airway cell line, A549. At concentrations of 25 microg/ml, diesel particulate matter induced the formation of multinucleate cells. In cells treated with a mixture o...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/sj.icb.7100109
更新日期:2007-11-01 00:00:00
abstract::The NK gene complex (NKC) on mouse chromosome 6 encodes receptors that are expressed on NK cells, such as Ly49H, and is involved in regulating NK cell control of virus infections, such as murine cytomegalovirus (MCMV). In the present study, we investigated the level of allelic heterogeneity in NKC loci in populations ...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/j.1440-1711.2005.01311.x
更新日期:2005-04-01 00:00:00
abstract::The HECT-type E3 ligase Itch is increasingly being shown to have a vital role in immune regulation. Itch deficiency leads to deleterious inflammatory disorders both in mice and humans. By adding ubiquitin to the key signaling intermediates, Itch functions as a critical regulator of lymphocyte-cell activation, differen...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.2014.118
更新日期:2015-05-01 00:00:00
abstract::Tumour necrosis factor (TNF) is a highly potent, proinflammatory cytokine with broad-ranging functions from the regulation of endothelial cell adhesion molecules to facilitate entry of leucocytes into tissues, to direct induction of cellular cytotoxicity. This diversity of function potentially attributable to TNF in t...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.1996.77
更新日期:1996-10-01 00:00:00
abstract::Two related folate antagonists aminopterin (AMN) and methotrexate (MTX) were used to produce drug-antibody conjugates and their tumouricidal effects compared in vitro and in vivo. Active ester derivatives were produced with the use of N-hydroxysuccinimide (NHS) and covalently coupled to monoclonal antibodies (MoAb) re...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1987.57
更新日期:1987-12-01 00:00:00
abstract::CD8(+) T cells kill pancreatic β-cells in a cell-cell contact-dependent mechanism in the non-obese diabetic mouse. CD4(+) T lymphocytes are also able to kill pancreatic β-cells, but they do not directly contact β-cells and may use another cell type as the actual cytotoxic cell. Natural killer (NK) cells could have thi...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2011.16
更新日期:2012-02-01 00:00:00
abstract::Genetic fusion of tandem repeats of the complement molecule C3d has been shown to considerably enhance immune responses to genetic vaccines. We have investigated the applicability of this approach to augment humoral immune responses toward vaccines delivered by recombinant adeno-associated virus (AAV) vectors. C3d(3)-...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2009.92
更新日期:2010-02-01 00:00:00
abstract::The mucosal system is the first line of defense against many pathogens. It is continuously exposed to dietary and microbial antigens, and thus the host must maintain a homeostatic environment between commensal microbiota and pathogenic infections. Following infections and inflammatory events, a rapid innate immune res...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.2012.13
更新日期:2012-05-01 00:00:00
abstract::This paper reports the isolation and characterization of sheep umbilical vein endothelial cells (ShUVEC) and examines the kinetics of the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In culture, the cells demonstrate the classical endothelial cell phenot...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1997.4
更新日期:1997-02-01 00:00:00
abstract::Over the past few years a great deal of research has examined how T cell-dependent immune responses are initiated and subsequently regulated. Ligation of the TCR with an antigenic peptide bound to an MHC protein on a professional APC provides the crucial antigen-specific stimulus required for T cell activation. Intera...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1711.1999.00795.x
更新日期:1999-02-01 00:00:00
abstract::Substance abuse is a growing world-wide problem. The big four drugs of abuse that might lend themselves to immunotherapy are nicotine, cocaine, morphine/heroin and methamphetamine. Tobacco abuse has a well-known enormous impact on major chronic cardiovascular and pulmonary diseases, while the last three, aside from th...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.2009.17
更新日期:2009-05-01 00:00:00
abstract::The present paper describes a comparative analysis of light chains associated with primary and secondary IgM, as well as with secondary IgG antibodies to fluorescein, undertaken in order to explore the relationship between light chain somatic hypermutation and the isotype switch. The data reveal a disparity in the fre...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.1440-1711.2000.00903.x
更新日期:2000-06-01 00:00:00
abstract::Variola virus, the causative agent of smallpox, is a member of the poxvirus family and one of the most virulent human pathogens known. Although smallpox was eradicated almost 30 years ago, it is not understood why the mortality rates associated with the disease were high, why some patients recovered, and what constitu...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/sj.icb.7100033
更新日期:2007-02-01 00:00:00
abstract::Early pregnancy factor (EPF), an extracellular chaperonin 10 homologue, has immunosuppressive and growth factor properties. In order to carry out more extensive studies on the in vivo characteristics of EPF, a recombinant form of the molecule has been prepared. Recombinant human EPF (rEPF) was expressed in Escherichia...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.1440-1711.2000.00951.x
更新日期:2000-12-01 00:00:00
abstract::The relationship between interleukin-1 (IL-1) and interleukin-2 (IL-2) production and immunophenotype marker profiles was studied in a panel of 29 leukaemia and human T cell lymphotropic virus-1 (HTLV-1)-transformed T cell lines. Culture supernatants from six of the 29 T cell lines tested increased IL-2 production by ...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1993.56
更新日期:1993-12-01 00:00:00
abstract::S100A8 and S100A9 are myeloid cell-derived proteins that are elevated in several types of inflammatory lung disorders. Pro- and anti-inflammatory properties are reported and these proteins are proposed to activate TLR4. S100A8 and S100A9 can function separately, likely through distinct receptors but a systematic compa...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2017.2
更新日期:2017-05-01 00:00:00
abstract::Ikaros, Aiolos and Helios encode zinc finger transcription factors that are important regulators of lymphoid development and differentiation. These proteins are involved in the control of gene expression and when associated with nuclear complexes, participate in nucleosome remodeling. Because differential splicing pro...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1711.2003.01159.x
更新日期:2003-06-01 00:00:00
abstract::B and T lymphocyte attenuator (BTLA) is an important negative regulator of T-cell activation. T-cell activation involves partitioning of receptors into discrete membrane compartments known as lipid rafts and the formation of an immunological synapse (IS) between the T cell and antigen-presenting cell (APC). Here we sh...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/sj.icb.7100087
更新日期:2007-11-01 00:00:00
abstract::NKT cells are a minor subset of T cells that have important roles in controlling immune responses in disease states including cancer, autoimmunity and pathogenic infections. In contrast to conventional T cells, NKT cells express an invariant TCR and respond to glycolipids presented by CD1d. In this study, we sought to...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/j.1440-1711.2005.01396.x
更新日期:2006-02-01 00:00:00
abstract::The Australian populations of rainbow trout (Onchorhynchus mykiss) and Atlantic salmon (Salmo salar) were found to have similar immunological responses to local strains of Vibrio anguillarum as those reported for the more genetically diverse populations of these fish and strains of V. anguillarum found in the Northern...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1992.51
更新日期:1992-12-01 00:00:00
abstract::FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that express...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2015.90
更新日期:2016-03-01 00:00:00
abstract::Increase in the practice of sport by more and more numerous people in the Western countries is associated with an increase in muscle injuries, and in demand for improving muscle function and acceleration of muscle recovery after damage. Most of the treatments used target inflammation. Indeed, several lines of experime...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.2015.97
更新日期:2016-02-01 00:00:00
abstract::Our earlier studies have demonstrated that gonadotropin-releasing hormone (GnRH) agonists suppress immune system function in female mice. No systematic studies regarding the effect of gender on immune system function following GnRH agonist treatment, however, have been reported. This study, therefore, investigated seq...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1996.18
更新日期:1996-04-01 00:00:00