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t cell repertoire

Rob R H van den Brom, Kornelis S M van der Geest, Elisabeth Brouwer, Geke A P Hospers, Annemieke M H Boots
The biological behavior of melanoma is unfavorable in the elderly when compared to young subjects. We hypothesized that differences in T-cell responses might underlie the distinct behavior of melanoma in young and old melanoma patients. Therefore, we investigated the circulating T-cell compartment of 34 patients with metastatic melanoma and 42 controls, which were classified as either young or old. Absolute numbers of CD4+ T cells were decreased in young and old melanoma patients when compared to the age-matched control groups...
March 15, 2018: Cancer Immunology, Immunotherapy: CII
Holger Winkels, Erik Ehinger, Melanie Vassallo, Konrad Buscher, Huy Dinh, Kouji Kobiyama, Anouk Hamers, Clément Cochain, Ehsan Vafadarnejad, Antoine-Emmanuel Saliba, Alma Zernecke, Akula Pramod, Amlan Ghosh, Nathaly Anto Michel, Natalie Hoppe, Ingo Hilgendorf, Andreas Zirlik, Catherine Hedrick, Klaus Ley, Dennis Wolf
<u>Rationale:</u> Atherosclerosis is a chronic inflammatory disease that is driven by the interplay of pro- and anti-inflammatory leukocytes in the aorta. Yet, the phenotypic and transcriptional diversity of aortic leukocytes is only poorly understood. <u>Objective:</u> We characterized leukocytes from healthy and atherosclerotic mouse aortas in-depth by single cell RNA-sequencing (scRNAseq) and mass cytometry (CyTOF) to define an atlas of the immune cell landscape in atherosclerosis...
March 15, 2018: Circulation Research
Taigo Kato, Tatsuo Matsuda, Yuji Ikeda, Jae-Hyun Park, Matthias Leisegang, Sachiko Yoshimura, Tetsuro Hikichi, Makiko Harada, Makda Zewde, Sho Sato, Kosei Hasegawa, Kazuma Kiyotani, Yusuke Nakamura
Neoantigens are the main targets of tumor-specific T cells reactivated by immune checkpoint-blocking antibodies or when using tumor-infiltrating T cells for adoptive therapy. While cancers often accumulate hundreds of mutations and harbor several immunogenic neoantigens, the repertoire of mutation-specific T cells in patients might be restricted. To bypass suboptimal conditions, which impede the reactivation of existing T cells or the priming of neoantigen-specific T cells in a patient, we employ T cells of healthy donors with an overlapping HLA repertoire to target cancer neoantigens...
February 16, 2018: Oncotarget
Phoebe Lin
PURPOSE OF REVIEW: The intestinal commensal microbiota are important in shaping immune cell repertoire and are influenced by host genetics. Because of this intricate interaction, an intestinal dysbiosis has been associated with multiple immune-mediated polygenic diseases. This review summarizes the literature on how alterations in the intestinal microbiota contribute to immune-mediated ocular disease, and how to potentially target the gut microbiome for therapeutic benefit. RECENT FINDINGS: Several groups have demonstrated the importance of the intestinal microbiome in uveitis pathogenesis...
March 13, 2018: Current Opinion in Ophthalmology
Taku Kuwabara, Yukihide Matsui, Fumio Ishikawa, Motonari Kondo
The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4⁺ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions...
March 12, 2018: International Journal of Molecular Sciences
Y S Tan, K Sansanaphongpricha, M E P Prince, D Sun, G T Wolf, Y L Lei
The recent Food and Drug Administration's approval of monoclonal antibodies targeting immune checkpoint receptors (ICRs) for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) offers exciting promise to improve patient outcome and reduce morbidities. A favorable response to ICR blockade relies on an extensive collection of preexisting tumor-specific T cells in the tumor microenvironment (TME). ICR blockade reinvigorates exhausted CD8+ T cells and enhances immune killing. However, resistance to ICR blockade is observed in about 85% of patients with HNSCC, therefore highlighting the importance of characterizing the mechanisms underlying HNSCC immune escape and exploring combinatorial strategies to sensitize hypoimmunogenic cold HNSCC to ICR inhibition...
March 1, 2018: Journal of Dental Research
Kok Fei Chan, Benjamin S Gully, Stephanie Gras, Dennis X Beringer, Lars Kjer-Nielsen, Jonathan Cebon, James McCluskey, Weisan Chen, Jamie Rossjohn
Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (>10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4+ TRAJ21+ -TRBV28+ TRBJ2-3+ and TRAV4+ TRAJ8+ -TRBV9+ TRBJ2-1+ ), originating from a polyclonal T-cell repertoire, bind to HLA-B*07:02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-160-72 ...
March 12, 2018: Nature Communications
Ke-Zheng Dai, James C Ryan, Christian Naper, John T Vaage
Early studies indicate that rats may have a repertoire of MHC class Ib-reactive Ly49 stimulatory receptors capable of mounting memory-like NK cell alloresponses. In this article, we provide molecular and functional evidence for this assumption. Pairs of Ly49 receptors with sequence similarities in the lectin-like domains, but with opposing signaling functions, showed specificity for ligands with class Ia-like structural features encoded from the first telomeric MHC class Ib gene cluster, RT1-CE , which is syntenic with the H2-D/H2-L/H2-Q cluster in mice...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
John J Miles, Mai Ping Tan, Garry Dolton, Emily Sj Edwards, Sarah Ae Galloway, Bruno Laugel, Mathew Clement, Julia Makinde, Kristin Ladell, Katherine K Matthews, Thomas S Watkins, Katie Tungatt, Yide Wong, Han Siean Lee, Richard J Clark, Johanne M Pentier, Meriem Attaf, Anya Lissina, Ann Ager, Awen Gallimore, Pierre J Rizkallah, Stephanie Gras, Jamie Rossjohn, Scott R Burrows, David K Cole, David A Price, Andrew K Sewell
Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic "mimics" using subunits that do not exist in the natural world. We developed a platform based on D-amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus...
March 12, 2018: Journal of Clinical Investigation
Esteban Arrieta-Bolaños, Pietro Crivello, Maximilian Metzing, Thuja Meurer, Müberra Ahci, Julie Rytlewski, Marissa Vignali, Erik Yusko, Peter van Balen, Peter A Horn, J H Frederik Falkenburg, Katharina Fleischhauer
T cell alloreactivity is mediated by a self-human leukocyte antigen (HLA)-restricted T cell receptor (TCR) repertoire able to recognize both structurally similar and dissimilar allogeneic HLA molecules (i.e., differing by a single or several amino acids in their peptide-binding groove). We hypothesized that thymic selection on self-HLA molecules could have an indirect impact on the size and diversity of the alloreactive response. To test this possibility, we used TCR Vβ immunophenotyping and immunosequencing technology in a model of alloreactivity between self-HLA selected T cells and allogeneic HLA-DPB1 (DPB1) differing from self-DPB1*04:02 by a single (DPB1*02:01) or several (DPB1*09:01) amino acids in the peptide-binding groove...
2018: Frontiers in Immunology
Kostas Patas, Anne Willing, Cüneyt Demiralay, Jan Broder Engler, Andreea Lupu, Caren Ramien, Tobias Schäfer, Christian Gach, Laura Stumm, Kenneth Chan, Marissa Vignali, Petra C Arck, Manuel A Friese, Ole Pless, Klaus Wiedemann, Agorastos Agorastos, Stefan M Gold
While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD) is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR) repertoire in MDD. For this cross-sectional case-control study, we recruited antidepressant-free patients with MDD without any somatic or psychiatric comorbidities ( n  = 20), who were individually matched for sex, age, body mass index, and smoking status to a non-depressed control subject ( n  = 20)...
2018: Frontiers in Immunology
Enkelejda Miho, Alexander Yermanos, Cédric R Weber, Christoph T Berger, Sai T Reddy, Victor Greiff
The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV). Adaptive immune receptor repertoire sequencing (AIRR-seq) has driven the quantitative and molecular-level profiling of immune repertoires, thereby revealing the high-dimensional complexity of the immune receptor sequence landscape...
2018: Frontiers in Immunology
Pedro Santos E Sousa, Séverine Ciré, Thomas Conlan, Laura Jardine, Claire Tkacz, Ivana R Ferrer, Cara Lomas, Sophie Ward, Heather West, Simone Dertschnig, Sven Blobner, Terry K Means, Stephen Henderson, Daniel H Kaplan, Matthew Collin, Vincent Plagnol, Clare L Bennett, Ronjon Chakraverty
Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic stem cell transplantation induced by the influx of donor-derived effector T cells (TE) into peripheral tissues. Current treatment strategies rely on targeting systemic T cells; however, the precise location and nature of instructions that program TE to become pathogenic and trigger injury are unknown. We therefore used weighted gene coexpression network analysis to construct an unbiased spatial map of TE differentiation during the evolution of GVHD and identified wide variation in effector programs in mice and humans according to location...
March 8, 2018: JCI Insight
Alexei F Kirkin, Karine N Dzhandzhugazyan, Per Guldberg, Johnny Jon Fang, Rikke S Andersen, Christina Dahl, Jann Mortensen, Tim Lundby, Aase Wagner, Ian Law, Helle Broholm, Line Madsen, Christer Lundell-Ek, Morten F Gjerstorff, Henrik J Ditzel, Martin R Jensen, Walter Fischer
In cancer cells, cancer/testis (CT) antigens become epigenetically derepressed through DNA demethylation and constitute attractive targets for cancer immunotherapy. Here we report that activated CD4+ T helper cells treated with a DNA-demethylating agent express a broad repertoire of endogenous CT antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes (CTLs) and natural killer cells. In vitro, activated CTLs induce HLA-restricted lysis of tumor cells of different histological types, as well as cells expressing single CT antigens...
March 6, 2018: Nature Communications
Moniek A de Witte, Dhifaf Sarhan, Zachary Davis, Martin Felices, Daniel A Vallera, Peter Hinderlie, Julie Curtsinger, Sarah Cooley, John Wagner, Jurgen Kuball, Jeffrey S Miller
Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HCT). NK cells and γδ T cells reconstitute early after allo-HCT, contribute to tumor immunosurveillance via MHC independent mechanisms and do not induce graft-versus-host disease (GVHD). Here we performed a quantitative and qualitative analysis of the NK and γδ T cell repertoire in healthy individuals, recipients of HLA-matched sibling or unrelated donor allo-HCT (MSD/MUD-HCT) and umbilical cord blood-HCT (UCB-HCT)...
March 2, 2018: Biology of Blood and Marrow Transplantation
Chaofei Cheng, Bei Wang, Lei Gao, Jianmin Liu, Xinchun Chen, He Huang, Zhendong Zhao
Tuberculosis (TB) is a severe global threat to human health. The immune protection initiated by γδ T cells play an important role in mycobacterial infection. Vaccines for Mycobacterium tuberculosis (Mtb) based on γδ T cells provide a novel approach for TB control. In our previous studies, we found a preponderant complementarity-determining region 3 (CDR3) sequence of the γδ T cell receptor (TCR) in TB patients, and successfully identified a tuberculosis antigen that can effectively activate γδ T cells with a reverse genetic strategy...
March 2, 2018: Scientific Reports
Bruno Cerqueira-Rodrigues, Ana Mendes, Margarida Correia-Neves, Claudia Nobrega
CD4+ T cells are essential players for the control of mycobacterial infections. Several mycobacterial antigens have been identified for eliciting a relevant CD4+ T cell mediated-immune response, and numerous studies explored this issue in the context of Mycobacterium tuberculosis infection. Antigen 85 (Ag85), a highly conserved protein across Mycobacterium species, is secreted at the early phase of M. tuberculosis infection leading to the proliferation of Ag85-specific CD4+ T cells. However, in the context of Mycobacterium avium infection, little is known about the expression of this antigen and the elicited immune response...
2018: PloS One
Véronique Schulten, Luise Westernberg, Giovanni Birrueta, John Sidney, Sinu Paul, Paula Busse, Bjoern Peters, Alessandro Sette
Mouse allergy has become increasingly common, mainly affecting laboratory workers and inner-city households. To date, only one major allergen, namely Mus m 1, has been described. We sought to identify T cell targets in mouse allergic patients. PBMC from allergic donors were expanded with either murine urine or epithelial extract and subsequently screened for cytokine production (IL-5 and IFNγ) in response to overlapping peptides spanning the entire Mus m 1 sequence, peptides from various Mus m 1 isoforms [major urinary proteins (MUPs)], peptides from mouse orthologs of known allergens from other mammalian species and peptides from proteins identified by immunoproteomic analysis of IgE/IgG immunoblots of mouse urine and epithelial extracts...
2018: Frontiers in Immunology
Kieran D James, William E Jenkinson, Graham Anderson
T-cells bearing the αβTCR play a vital role in defending the host against foreign pathogens and malignant transformation of self. Importantly, T-cells are required to remain tolerant to the host's own cells and tissues in order to prevent self-reactive responses that can lead to autoimmune disease. T-cells achieve the capacity for self/nonself discrimination by undergoing a highly selective and rigorous developmental program during their maturation in the thymus. This organ is unique in its ability to support a program of T-cell development that ensures the establishment of a functionally diverse αβTCR repertoire within the peripheral T-cell pool...
February 27, 2018: Journal of Leukocyte Biology
Xiao Liu, Jinghua Wu
The diversity of T and B cells in terms of their receptor sequences is huge in the vertebrate's immune system and provides broad protection against the vast diversity of pathogens. Immune repertoire is defined as the sum of T cell receptors and B cell receptors (also named immunoglobulin) that makes the organism's adaptive immune system. Before the emergence of high-throughput sequencing, the studies on immune repertoire were limited by the underdeveloped methodologies, since it was impossible to capture the whole picture by the low-throughput tools...
February 27, 2018: Cell Biology and Toxicology
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