Mixed functional characteristics correlating with TCR-ligand koff-rate of MHC-tetramer reactive T cells within the naive T-cell repertoire

2013 ◽  
Vol 43 (11) ◽  
pp. 3038-3050 ◽  
Author(s):  
Pleun Hombrink ◽  
Yotam Raz ◽  
Michel G. D. Kester ◽  
Renate de Boer ◽  
Bianca Weißbrich ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Repertoire ◽  
Functional Characteristics ◽  
Cell Repertoire ◽  
Naïve T Cell ◽  
Naive T Cell

scholarly journals Drug and Chemical Allergy: A Role for a Specific Naive T-Cell Repertoire?

2021 ◽  
Vol 12 ◽  
Author(s):  
Rami Bechara ◽  
Alexia Feray ◽  
Marc Pallardy
Keyword(s):  
T Cells ◽  
T Cell ◽  
Rare Event ◽  
Thymic Selection ◽  
T Cell Epitopes ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Naïve T Cell ◽  
Naive T Cell ◽  
Selection Of

Allergic reactions to drugs and chemicals are mediated by an adaptive immune response involving specific T cells. During thymic selection, T cells that have not yet encountered their cognate antigen are considered naive T cells. Due to the artificial nature of drug/chemical-T-cell epitopes, it is not clear whether thymic selection of drug/chemical-specific T cells is a common phenomenon or remains limited to few donors or simply does not exist, suggesting T-cell receptor (TCR) cross-reactivity with other antigens. Selection of drug/chemical-specific T cells could be a relatively rare event accounting for the low occurrence of drug allergy. On the other hand, a large T-cell repertoire found in multiple donors would underline the potential of a drug/chemical to be recognized by many donors. Recent observations raise the hypothesis that not only the drug/chemical, but also parts of the haptenated protein or peptides may constitute the important structural determinants for antigen recognition by the TCR. These observations may also suggest that in the case of drug/chemical allergy, the T-cell repertoire results from particular properties of certain TCR to recognize hapten-modified peptides without need for previous thymic selection. The aim of this review is to address the existence and the role of a naive T-cell repertoire in drug and chemical allergy. Understanding this role has the potential to reveal efficient strategies not only for allergy diagnosis but also for prediction of the immunogenic potential of new chemicals.

scholarly journals T cell immunodominance is dictated by the positively selecting self-peptide

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Wan-Lin Lo ◽  
Benjamin D Solomon ◽  
David L Donermeyer ◽  
Chyi-Song Hsieh ◽  
Paul M Allen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
T Cell Response ◽  
Cell Precursor ◽  
Cell Repertoire ◽  
Precursor Frequency ◽  
Naïve T Cell ◽  
Naive T Cell

Naive T cell precursor frequency determines the magnitude of immunodominance. While a broad T cell repertoire requires diverse positively selecting self-peptides, how a single positively selecting ligand influences naive T cell precursor frequency remains undefined. We generated a transgenic mouse expressing a naturally occurring self-peptide, gp250, that positively selects an MCC-specific TCR, AND, as the only MHC class II I-Ek ligand to study the MCC highly organized immunodominance hierarchy. The single gp250/I-Ek ligand greatly enhanced MCC-tetramer+ CD4+ T cells, and skewed MCC-tetramer+ population toward V11α+Vβ3+, a major TCR pair in MCC-specific immunodominance. The gp250-selected V11α+Vβ3+ CD4+ T cells had a significantly increased frequency of conserved MCC-preferred CDR3 features. Our studies establish a direct and causal relationship between a selecting self-peptide and the specificity of the selected TCRs. Thus, an immunodominant T cell response can be due to a dominant positively selecting self-peptide.

scholarly journals Stochastic competitive exclusion in the maintenance of the naïve T cell repertoire

2010 ◽  
Vol 265 (3) ◽  
pp. 396-410 ◽  
Author(s):  
Emily R. Stirk ◽  
Grant Lythe ◽  
Hugo A. van den Berg ◽  
Carmen Molina-París
Keyword(s):  
T Cell ◽  
Competitive Exclusion ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Naïve T Cell ◽  
Naive T Cell

scholarly journals Convergent recombination shapes the clonotypic landscape of the naive T-cell repertoire

2010 ◽  
Vol 107 (45) ◽  
pp. 19414-19419 ◽  
Author(s):  
M. F. Quigley ◽  
H. Y. Greenaway ◽  
V. Venturi ◽  
R. Lindsay ◽  
K. M. Quinn ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Naïve T Cell ◽  
Naive T Cell

scholarly journals Naive T Cell Repertoire Skewing in HLA-A2 Individuals by a Specialized Rearrangement Mechanism Results in Public Memory Clonotypes

2011 ◽  
Vol 186 (5) ◽  
pp. 2970-2977 ◽  
Author(s):  
Maryam Yassai ◽  
Dmitry Bosenko ◽  
Melissa Unruh ◽  
Gregory Zacharias ◽  
Erica Reed ◽  
...  
Keyword(s):  
T Cell ◽  
Public Memory ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Rearrangement Mechanism ◽  
Naïve T Cell ◽  
Naive T Cell

scholarly journals Polyclonal expansion of TCR Vbeta 21.3+ CD4+ and CD8+ T cells is a hallmark of Multisystem Inflammatory Syndrome in Children

2021 ◽  
Vol 6 (59) ◽  
pp. eabh1516
Author(s):  
Marion Moreews ◽  
Kenz Le Gouge ◽  
Samira Khaldi-Plassart ◽  
Rémi Pescarmona ◽  
Anne-Laure Mathieu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
Healthy Children ◽  
Antigenic Peptides ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Hla Dr ◽  
T Cell Expansion ◽  
Inflammatory Syndrome

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vβ21.3 T cell receptor β chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vβ21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vβ21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

scholarly journals VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance

Science ◽  
2020 ◽  
Vol 367 (6475) ◽  
pp. eaay0524 ◽  
Author(s):  
Mohamed A. ElTanbouly ◽  
Yanding Zhao ◽  
Elizabeth Nowak ◽  
Jiannan Li ◽  
Evelien Schaafsma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Subset ◽  
Peripheral Tolerance ◽  
Cell Immune Response ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Naïve T Cell ◽  
Naive T Cell

Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit the development of autoimmunity. Unlike all other NCRs that are expressed on activated T lymphocytes, V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is expressed on naïve T cells. We report an unexpected heterogeneity within the naïve T cell compartment in mice, where loss of VISTA disrupted the major quiescent naïve T cell subset and enhanced self-reactivity. Agonistic VISTA engagement increased T cell tolerance by promoting antigen-induced peripheral T cell deletion. Although a critical player in naïve T cell homeostasis, the ability of VISTA to restrain naïve T cell responses was lost under inflammatory conditions. VISTA is therefore a distinctive NCR of naïve T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance.

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