scholarly journals TCR Transgenic Mice: A Valuable Tool for Studying Viral Immunopathogenesis Mechanisms

2020 ◽  
Vol 21 (24) ◽  
pp. 9690
Author(s):  
Yong-Bin Cho ◽  
In-Gu Lee ◽  
Yong-Hyun Joo ◽  
So-Hee Hong ◽  
Young-Jin Seo
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Receptor ◽  
Global Economy ◽  
Viral Infections ◽  
Cell Receptor ◽  
Cell Responses ◽  
Significant Burden ◽  
Underlying Mechanisms ◽  
Remarkable Progress

Viral infectious diseases are a significant burden on public health and the global economy, and new viral threats emerge continuously. Since CD4+ and CD8+ T cell responses are essential to eliminating viruses, it is important to understand the underlying mechanisms of anti-viral T cell-mediated immunopathogenesis during viral infections. Remarkable progress in transgenic (Tg) techniques has enabled scientists to more readily understand the mechanisms of viral pathogenesis. T cell receptor (TCR) Tg mice are extremely useful in studying T cell-mediated immune responses because the majority of T cells in these mice express specific TCRs for partner antigens. In this review, we discuss the important studies utilizing TCR Tg mice to unveil underlying mechanisms of T cell-mediated immunopathogenesis during viral infections.

scholarly journals A vaccine targeting mutant IDH1 in newly diagnosed glioma

Nature ◽  
2021 ◽  
Author(s):  
Michael Platten ◽  
Lukas Bunse ◽  
Antje Wick ◽  
Theresa Bunse ◽  
Lucian Le Cornet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cell Receptor ◽  
T Helper Cell ◽  
Newly Diagnosed ◽  
T Helper ◽  
Cell Responses ◽  
Idh1 R132h

AbstractMutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma1–3. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II4,5. An IDH1(R132H)-specific peptide vaccine (IDH1-vac) induces specific therapeutic T helper cell responses that are effective against IDH1(R132H)+ tumours in syngeneic MHC-humanized mice4,6–8. Here we describe a multicentre, single-arm, open-label, first-in-humans phase I trial that we carried out in 33 patients with newly diagnosed World Health Organization grade 3 and 4 IDH1(R132H)+ astrocytomas (Neurooncology Working Group of the German Cancer Society trial 16 (NOA16), ClinicalTrials.gov identifier NCT02454634). The trial met its primary safety endpoint, with vaccine-related adverse events restricted to grade 1. Vaccine-induced immune responses were observed in 93.3% of patients across multiple MHC alleles. Three-year progression-free and death-free rates were 0.63 and 0.84, respectively. Patients with immune responses showed a two-year progression-free rate of 0.82. Two patients without an immune response showed tumour progression within two years of first diagnosis. A mutation-specificity score that incorporates the duration and level of vaccine-induced IDH1(R132H)-specific T cell responses was associated with intratumoral presentation of the IDH1(R132H) neoantigen in pre-treatment tumour tissue. There was a high frequency of pseudoprogression, which indicates intratumoral inflammatory reactions. Pseudoprogression was associated with increased vaccine-induced peripheral T cell responses. Combined single-cell RNA and T cell receptor sequencing showed that tumour-infiltrating CD40LG+ and CXCL13+ T helper cell clusters in a patient with pseudoprogression were dominated by a single IDH1(R132H)-reactive T cell receptor.

Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling

2021 ◽  
Vol 6 (66) ◽  
Author(s):  
Puspa Thapa ◽  
Rebecca S. Guyer ◽  
Alexander Y. Yang ◽  
Christopher A. Parks ◽  
Todd M. Brusko ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
T Cell Receptor Signaling ◽  
Cell Receptor Signaling

scholarly journals A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires

2021 ◽  
Vol 12 ◽  
Author(s):  
Valentina Ceglia ◽  
Erin J. Kelley ◽  
Annalee S. Boyle ◽  
Sandra Zurawski ◽  
Heather L. Mead ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
Protein Antigens ◽  
Cell Responses ◽  
Tcr Repertoire ◽  
Receptor Clusters ◽  
Theoretical Sensitivity

Common approaches for monitoring T cell responses are limited in their multiplexity and sensitivity. In contrast, deep sequencing of the T Cell Receptor (TCR) repertoire provides a global view that is limited only in terms of theoretical sensitivity due to the depth of available sampling; however, the assignment of antigen specificities within TCR repertoires has become a bottleneck. This study combines antigen-driven expansion, deep TCR sequencing, and a novel analysis framework to show that homologous ‘Clusters of Expanded TCRs (CETs)’ can be confidently identified without cell isolation, and assigned to antigen against a background of non-specific clones. We show that clonotypes within each CET respond to the same epitope, and that protein antigens stimulate multiple CETs reactive to constituent peptides. Finally, we demonstrate the personalized assignment of antigen-specificity to rare clones within fully-diverse uncultured repertoires. The method presented here may be used to monitor T cell responses to vaccination and immunotherapy with high fidelity.

scholarly journals The Hepatitis C Virus Core Protein Modulates T Cell Responses by Inducing Spontaneous and Altering T-cell Receptor-triggered Ca2+Oscillations

2003 ◽  
Vol 278 (21) ◽  
pp. 18877-18883 ◽  
Author(s):  
Anders Bergqvist ◽  
Sara Sundström ◽  
Lina Y. Dimberg ◽  
Erik Gylfe ◽  
Maria G. Masucci
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Receptor ◽  
Core Protein ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Cell Responses ◽  
Virus Core

scholarly journals Neonates Mount Robust and Protective Adult-Like CD8+-T-Cell Responses to DNA Vaccines

2002 ◽  
Vol 76 (23) ◽  
pp. 11911-11919 ◽  
Author(s):  
Jie Zhang ◽  
Nicole Silvestri ◽  
J. Lindsay Whitton ◽  
Daniel E. Hassett
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Viral Infections ◽  
Dna Vaccines ◽  
Neonatal Period ◽  
Cytotoxic T Cells ◽  
Lymphocytic Choriomeningitis ◽  
Cell Responses ◽  
Rapid Induction

ABSTRACT Neonates are thought to mount less vigorous adaptive immune responses than adults to antigens and infectious agents. This concept has led to a delay in the administration of many currently available vaccines until late infancy or early childhood. It has recently been shown that vaccines composed of plasmid DNA can induce both humoral and cell-mediated antimicrobial immunity when administered within hours of birth. In most of these studies, immune responses were measured weeks or months after the initial vaccination, and it is therefore questionable whether the observed responses were actually the result of priming of splenocytes within the neonatal period. Here we show that DNA vaccination at birth results in the rapid induction of antigen-specific CD8+ T cells within neonatal life. Analyses of T-cell effector functions critical for the resolution of many viral infections revealed that neonatal and adult CD8+ T cells produce similar arrays of cytokines. Furthermore, the avidities of neonatal and adult CD8+ T cells for peptide and the rapidity with which they upregulate cytokine production after recall encounters with antigen are similar. Protective immunity against the arenavirus lymphocytic choriomeningitis virus, which is mediated by CD8+ cytotoxic T cells, is also rapidly acquired within the neonatal period. Collectively these data imply that, at least in the case of CD8+ T cells, neonates are not as immunodeficient as previously supposed and that DNA vaccines may be an effective and safe means of providing critical cell-mediated antiviral immunity extremely early in life.

scholarly journals CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

2017 ◽  
Vol 114 (51) ◽  
pp. E10956-E10964 ◽  
Author(s):  
Andrew Chancellor ◽  
Anna S. Tocheva ◽  
Chris Cave-Ayland ◽  
Liku Tezera ◽  
Andrew White ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Head Group ◽  
Computational Simulations ◽  
Functional Responses ◽  
Cell Responses ◽  
Group Movement

Tuberculosis (TB), caused byMycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in TB granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells.

scholarly journals Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses

2011 ◽  
Vol 108 (23) ◽  
pp. 9536-9541 ◽  
Author(s):  
E. B. Day ◽  
C. Guillonneau ◽  
S. Gras ◽  
N. L. La Gruta ◽  
D. A. A. Vignali ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Structural Basis ◽  
Cell Responses
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