High Precursor Frequency and Promiscuity in Αβ T Cell Receptor Pairing Underpin CD8+ T-Cell Responses to an Immunodominant SARS-CoV-2 Nucleocapsid Epitope

2020 ◽  
Author(s):  
Thi H. O. Nguyen ◽  
L. Rowntree ◽  
Jan Petersen ◽  
B. Chua ◽  
Luca Hensen ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Cell Responses ◽  
Precursor Frequency

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

scholarly journals Virus-specific CD8+ T-cell responses in mice transgenic for a T-cell receptor beta chain selected at random.

1994 ◽  
Vol 68 (5) ◽  
pp. 3065-3070 ◽  
Author(s):  
C Ewing ◽  
W Allan ◽  
K Daly ◽  
S Hou ◽  
G A Cole ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Beta Chain ◽  
Cell Responses ◽  
T Cell Receptor Beta ◽  
Receptor Beta

scholarly journals Narrowing of Human Influenza A Virus-Specific T Cell Receptor α and β Repertoires with Increasing Age

2015 ◽  
Vol 89 (8) ◽  
pp. 4102-4116 ◽  
Author(s):  
Anna Gil ◽  
Maryam B. Yassai ◽  
Yuri N. Naumov ◽  
Liisa K. Selin
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Influenza A Virus ◽  
Influenza A ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Cross Reactivity ◽  
Older Individuals ◽  
Cell Responses

ABSTRACTAlterations in memory CD8 T cell responses may contribute to the high morbidity and mortality caused by seasonal influenza A virus (IAV) infections in older individuals. We questioned whether memory CD8 responses to this nonpersistent virus, to which recurrent exposure with new strains is common, changed over time with increasing age. Here, we show a direct correlation between increasing age and narrowing of the HLA-A2-restricted IAV Vα and Vβ T cell repertoires specific to M1 residues 58 to 66 (M158–66), which simultaneously lead to oligoclonal expansions, including the usage of a single identical VA12-JA29 clonotype in all eight older donors. The Vα repertoire of older individuals also had longer CDR3 regions with increased usage of G/A runs, whose molecular flexibility may enhance T cell receptor (TCR) promiscuity. Collectively, these results suggest that CD8 memory T cell responses to nonpersistent viruses like IAV in humans are dynamic, and with aging there is a reduced diversity but a preferential retention of T cell repertoires with features of enhanced cross-reactivity.IMPORTANCEWith increasing age, the immune system undergoes drastic changes, and older individuals have declined resistance to infections. Vaccinations become less effective, and infection with influenza A virus in older individuals is associated with higher morbidity and mortality. Here, we questioned whether T cell responses directed against the highly conserved HLA-A2-restricted M158–66peptide of IAV evolves with increasing age. Specifically, we postulated that CD8 T cell repertoires narrow with recurrent exposure and may thus be less efficient in response to new infections with new strains of IAV. Detailed analyses of the VA and VB TCR repertoires simultaneously showed a direct correlation between increasing age and narrowing of the TCR repertoire. Features of the TCRs indicated potentially enhanced cross-reactivity in all older donors. In summary, T cell repertoire analysis in older individuals may be useful as one of the predictors of protection after vaccination.

scholarly journals Contribution of T cell receptor affinity to overall avidity for virus-specific CD8+ T cell responses

2005 ◽  
Vol 102 (32) ◽  
pp. 11432-11437 ◽  
Author(s):  
K. Kedzierska ◽  
N. L. La Gruta ◽  
M. P. Davenport ◽  
S. J. Turner ◽  
P. C. Doherty
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Receptor Affinity ◽  
Cell Responses

scholarly journals Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexandria C Wells ◽  
Keith A Daniels ◽  
Constance C Angelou ◽  
Eric Fagerberg ◽  
Amy S Burnside ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Cell Responses

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.

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 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.

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