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The Many Facets of the Regulation of TCR Signaling 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 2622

Special Issue Editors


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Guest Editor
Health Campus Immunology, Infectiology, and Inflammation, Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany
Interests: lymphocyte signaling; T-cell receptor signaling; Zap70; Lck; tyrosine kinases; T-cell activation; thymic development; natural products; immunomodulation
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Magdeburg Health Campus Immunology, Infectiology, and Inflammation, Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany
Interests: T cell
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

T cells are well-known for their importance in the orchestration of the adaptive immune response. Alterations in the function of T cells are at the basis of many inflammatory disorders including autoimmune diseases, allergy, transplant rejection, reperfusion injury, and cancer as well as in immunodeficiency. T-cell functions critically depend on signaling cascades triggered upon the engagement of the T-cell receptor (TCR). The experimental evidence accumulated over the past decades has demonstrated that the TCR regulates development, activation, differentiation, and homeostasis of T cells. How signaling via a single receptor can dictate different cellular outcomes has intrigued many researchers. It has become clearer that the intensity and the duration of TCR signaling and its integration with signaling cascades downstream of other cell surface receptors operate in concert to dictate the specific cell fate and response.

In this Special Issue, we invite investigators to submit original research or review articles on the many facets in the regulation of TCR signaling.

Topics include but are not limited to the following:

  • Dynamic changes of TCR conformation and initiation of TCR signaling
  • Orchestration of proximal signaling events
  • Propagation of TCR signaling and initiation of transcription
  • Signaling molecules: adaptors, kinases, phosphatases, etc.
  • Integration of TCR signaling: co-stimulatory molecules
  • Inhibition of TCR signaling
  • TCR signal strength and TCR signaling dynamics
  • Modeling of TCR signaling
  • Redox-mediated regulation of TCR signaling
  • Engineered TCRs: signaling via CARs

Prof. Dr. Luca Simeoni
Prof. Dr. Ursula Bommhardt 
Guest Editors

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Published Papers (1 paper)

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Research

15 pages, 2956 KiB  
Article
Y192 within the SH2 Domain of Lck Regulates TCR Signaling Downstream of PLC-γ1 and Thymic Selection
by Matthias Kästle, Camilla Merten, Roland Hartig, Carlos Plaza-Sirvent, Ingo Schmitz, Ursula Bommhardt, Burkhart Schraven and Luca Simeoni
Int. J. Mol. Sci. 2022, 23(13), 7271; https://doi.org/10.3390/ijms23137271 - 30 Jun 2022
Cited by 5 | Viewed by 2268
Abstract
Signaling via the TCR, which is initiated by the Src-family tyrosine kinase Lck, is crucial for the determination of cell fates in the thymus. Because of its pivotal role, ablation of Lck results in a profound block of T-cell development. Here, we show [...] Read more.
Signaling via the TCR, which is initiated by the Src-family tyrosine kinase Lck, is crucial for the determination of cell fates in the thymus. Because of its pivotal role, ablation of Lck results in a profound block of T-cell development. Here, we show that, in addition to its well-known function in the initiation of TCR signaling, Lck also acts at a more downstream level. This novel function of Lck is determined by the tyrosine residue (Y192) located in its SH2 domain. Thymocytes from knock-in mice expressing a phosphomimetic Y192E mutant of Lck initiate TCR signaling upon CD3 cross-linking up to the level of PLC-γ1 phosphorylation. However, the activation of downstream pathways including Ca2+ influx and phosphorylation of Erk1/2 are impaired. Accordingly, positive and negative selections are blocked in LckY192E knock-in mice. Collectively, our data indicate that Lck has a novel function downstream of PLCγ-1 in the regulation of thymocyte differentiation and selection. Full article
(This article belongs to the Special Issue The Many Facets of the Regulation of TCR Signaling 2.0)
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