ALTERED PEPTIDE LIGAND–INDUCED PARTIAL T CELL ACTIVATION: Molecular Mechanisms and Role in T Cell Biology

1996 ◽  
Vol 14 (1) ◽  
pp. 1-27 ◽  
Author(s):  
Joanne Sloan-Lancaster ◽  
Paul M. Allen
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Peptide Ligand ◽  
Altered Peptide Ligand ◽  
T Cell Biology

scholarly journals Computational properties of mitochondria in T cell activation and fate

Open Biology ◽  
2016 ◽  
Vol 6 (11) ◽  
pp. 160192 ◽  
Author(s):  
Roman Uzhachenko ◽  
Anil Shanker ◽  
Geneviève Dupont
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Pid Controller ◽  
Cell Activation ◽  
Digital Signal ◽  
Cell Life ◽  
T Cell Biology ◽  
Cellular Ca ◽  
Computational Properties

In this article, we review how mitochondrial Ca 2+ transport (mitochondrial Ca 2+ uptake and Na + /Ca 2+ exchange) is involved in T cell biology, including activation and differentiation through shaping cellular Ca 2+ signals. Based on recent observations, we propose that the Ca 2+ crosstalk between mitochondria, endoplasmic reticulum and cytoplasm may form a proportional–integral–derivative (PID) controller. This PID mechanism (which is well known in engineering) could be responsible for computing cellular decisions. In addition, we point out the importance of analogue and digital signal processing in T cell life and implication of mitochondrial Ca 2+ transport in this process.

A role of kinase inactive ZAP-70 in altered peptide ligand stimulated T cell activation

2006 ◽  
Vol 341 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Jeong-Ran Kim ◽  
Atsushi Irie ◽  
Hirotake Tsukamoto ◽  
Yasuharu Nishimura
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Peptide Ligand ◽  
Altered Peptide Ligand

scholarly journals The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function

2020 ◽  
Author(s):  
Bergithe E Oftedal ◽  
Stefano Maio ◽  
Adam Handel ◽  
Madeleine PJ White ◽  
Duncan Howie ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
T Cell Biology ◽  
Th2 Polarization ◽  
Cell Stress Response ◽  
And Function ◽  
Induced Changes

AbstractT cells rely for their development and function on the correct folding and turnover of proteins generated in response to a broad range of molecular cues. In the absence of the eukaryotic type II chaperonin complex, CCT, T cell activation induced changes in the proteome are compromised including the formation of nuclear actin filaments and the formation of a normal cell stress response. Consequently, thymocyte maturation and selection, and T cell homeostatic maintenance and receptor-mediated activation are severely impaired. Additionally, Th2 polarization digresses in the absence of CCT-controlled protein folding resulting paradoxically in continued IFN-γ expression. As a result, CCT-deficient T cells fail to generate an efficient immune protection against helminths as they are unable to sustain a coordinated recruitment of the innate and adaptive immune systems. These findings thus demonstrate that normal T cell biology is critically dependent on CCT-controlled proteostasis and that its absence is incompatible with protective immunity.

scholarly journals Immunomodulatory Effects of Polysaccharide from Marine FungusPhoma herbarumYS4108 on T Cells and Dendritic Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Song Chen ◽  
Ran Ding ◽  
Yan Zhou ◽  
Xian Zhang ◽  
Rui Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Interleukin 12 ◽  
Related Factors ◽  
Knock Out ◽  
Specific Immunity

YCP, as a kind of natural polysaccharides from the mycelium of marine filamentous fungusPhoma herbarumYS4108, has great antitumor potentialviaenhancement of host immune response, but little is known about the molecular mechanisms. In the present study, we mainly focused on the effects and mechanisms of YCP on the specific immunity mediated by dendritic cells (DCs) and T cells. T cell /DC activation-related factors including interferon- (IFN-)γ, interleukin-12 (IL-12), and IL-4 were examined with ELISA. Receptor knock-out mice and fluorescence-activated cell sorting are used to analyze the YCP-binding receptor of T cells and DCs. RT-PCR is utilized to measure MAGE-A3 for analyzing the tumor-specific killing effect. In our study, we demonstrated YCP can provide the second signal for T cell activation, proliferation, and IFN-γproduction through binding to toll-like receptor- (TLR-) 2 and TLR-4. YCP could effectively promote IL-12 secretion and expression of markers (CD80, CD86, and MHC II)viaTLR-4 on DCs. Antigen-specific immunity against mouse melanoma cells was strengthened through the activation of T cells and the enhancement of capacity of DCs by YCP. The data supported that YCP can exhibit specific immunomodulatory capacity mediated by T cells and DCs.

scholarly journals Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy

2021 ◽  
Vol 22 (19) ◽  
pp. 10800
Author(s):  
Shubhangi Gavali ◽  
Jianing Liu ◽  
Xinyi Li ◽  
Magdalena Paolino
Keyword(s):  
T Cell ◽  
Patient Outcomes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
Patient Treatment ◽  
Functional Roles ◽  
Protein Ubiquitination ◽  
Fine Tune

The advent of T-cell-based immunotherapy has remarkably transformed cancer patient treatment. Despite their success, the currently approved immunotherapeutic protocols still encounter limitations, cause toxicity, and give disparate patient outcomes. Thus, a deeper understanding of the molecular mechanisms of T-cell activation and inhibition is much needed to rationally expand targets and possibilities to improve immunotherapies. Protein ubiquitination downstream of immune signaling pathways is essential to fine-tune virtually all immune responses, in particular, the positive and negative regulation of T-cell activation. Numerous studies have demonstrated that deregulation of ubiquitin-dependent pathways can significantly alter T-cell activation and enhance antitumor responses. Consequently, researchers in academia and industry are actively developing technologies to selectively exploit ubiquitin-related enzymes for cancer therapeutics. In this review, we discuss the molecular and functional roles of ubiquitination in key T-cell activation and checkpoint inhibitory pathways to highlight the vast possibilities that targeting ubiquitination offers for advancing T-cell-based immunotherapies.

scholarly journals Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Jue Hou ◽  
Shuhui Wang ◽  
Dan Li ◽  
Lindsay N. Carpp ◽  
Tong Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Neutralizing Antibody ◽  
Activator Protein 1 ◽  
Successful Vaccine ◽  
Hiv 1 ◽  
Core Genes

Both vaccine “take” and neutralizing antibody (nAb) titer are historical correlates for vaccine-induced protection from smallpox. We analyzed a subset of samples from a phase 2a trial of three DNA/HIV-1 primes and a recombinant Tiantan vaccinia virus-vectored (rTV)/HIV-1 booster and found that a proportion of participants showed no anti-vaccinia nAb response to the rTV/HIV-1 booster, despite successful vaccine “take.” Using a rich transcriptomic and vaccinia-specific immunological dataset with fine kinetic sampling, we investigated the molecular mechanisms underlying nAb response. Blood transcription module analysis revealed the downregulation of the activator protein 1 (AP-1) pathway in responders, but not in non-responders, and the upregulation of T-cell activation in responders. Furthermore, transcriptional factor network reconstruction revealed the upregulation of AP-1 core genes at hour 4 and day 1 post-rTV/HIV-1 vaccination, followed by a downregulation from day 3 until day 28 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated on day 7 in non-responders. We speculate that persistent pro-inflammatory signaling early post-rTV/HIV-1 vaccination inhibits the nAb response.

scholarly journals Recognition of the Major Histocompatibility Complex Restriction Element Modulates CD8+ T Cell Specificity and Compensates for Loss of  T Cell Receptor Contacts with the Specific Peptide

1999 ◽  
Vol 189 (6) ◽  
pp. 883-894 ◽  
Author(s):  
Johan K. Sandberg ◽  
Klas Kärre ◽  
Rickard Glas
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Peptide Ligand ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Cell Specificity ◽  
Restriction Element

Triggering of a T cell requires interaction between its specific receptor (TCR) and a peptide antigen presented by a self–major histocompatibility complex (MHC) molecule. TCR recognition of self-MHC by itself falls below the threshold of detection in most systems due to low affinity. To study this interaction, we have used a read-out system in which antigen-specific effector T cells are confronted with targets expressing high levels of MHC compared with the selecting and priming environment. More specifically, the system is based on CD8+ T cells selected in an environment with subnormal levels of MHC class I in the absence of β2-microglobulin. We observe that the MHC restriction element can trigger viral peptide-specific T cells independently of the peptide ligand, provided there is an increase in self-MHC density. Peptide-independent triggering required at least four times the natural in vivo level of MHC expression. Furthermore, recognition of the restriction element at expression levels below this threshold was still enough to compensate for lack of affinity to peptides carrying alanine substitutions in major TCR contact residues. Thus, the specificity in TCR recognition and T cell activation is fine tuned by the avidity for self-MHC, and TCR avidities for peptide and MHC may substitute for each other. These results demonstrate a functional role for TCR avidity for self-MHC in tuning of T cell specificity, and support a role for cross-reactivity on “self” during T cell selection and activation.

scholarly journals Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Yury Rubtsov ◽  
Кirill Goryunov ◽  
Аndrey Romanov ◽  
Yulia Suzdaltseva ◽  
George Sharonov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Mixed Cultures ◽  
Activated T Cells

Mesenchymal stromal cells (MSC) control excessive inflammation and create a microenvironment for tissue repair protecting from chronic inflammation and tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory function in mixed cultures of human adipose-derived MSC with lymphocytes. Our data show that MSC promote unstimulated lymphocyte survival potentially by an increase in antigen presentation. Under inflammatory conditions, mimicked by stimulation of TCR in lymphocytes, MSC suppress activation and proliferation of stimulated T cells. Immunosuppression is accompanied by downregulation of IL-2Rαthat negatively affects the survival of activated T cells. MSC upregulate transcription of indolamine-2,3-dioxygenase (IDO) and inducible NO synthase (iNOS), which generate products negatively affecting T cell function. Both MSC and lymphocytes dramatically increase the surface ICAM-1 level in mixed cultures. Antibody-mediated blockage of surface ICAM-1 partially releases MSC-mediated immune suppression in vitro. Our data suggest that MSC have cell-intrinsic molecular programs depending on the inflammatory microenvironment. We speculate that MSC sense soluble factors and respond by surface ICAM-1 upregulation. ICAM-1 is involved in the control of T cell activation leading to immunosuppression or modest stimulation depending on the T cell status. Immunomodulation by MSC ranging from support of naive T cell survival to immunosuppression of activated T cells may affect the tissue microenvironment protecting from aberrant regeneration.

Cell Biology of T Cell Activation and Differentiation

2006 ◽  
pp. 217-274 ◽  
Author(s):  
María Angélica Santana ◽  
Fernando Esquivel‐Guadarrama
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation
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