Abstract
Full and productive activation of T lymphocytes relies on the simultaneous delivery of T cell receptor (TCR)- and coreceptor-derived signals. In naïve T cells engagement of the TCR alone causes anergy, while TCR triggering of preactivated T cells results in activation-induced cell death. Costimulatory signals are prominently mirrored by the activation of NF-κB, which needs input from the TCR as well as from coreceptors in order to be fully activated and to fulfil its crucial function in the immune response. Coreceptor-generated signals tightly control the duration and amplitude of the NF-κB response. The activation of IκB kinase (IKK) complex at the contact zone between a T cell and an antigen-presenting cell offers the unique opportunity to study the spatial organization of IKK activation. Recent studies indicate that coreceptor pathways influence the threshold activities of many signalling mediators and thus act on multiple layers of the NF-κB pathway.
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Abbreviations
- APC:
-
antigen-presenting cell
- CTLA4:
-
cytotoxic T lymphocyte antigen 4
- GEF:
-
guanine exchange factor
- GSK3:
-
glycogen synthase kinase 3
- HECT:
-
homology to E6-AP C terminus
- ICAM:
-
intercellular adhesion molecule
- ICOS:
-
inducible T cell costimulator
- IKK:
-
IκB kinase
- IL-2:
-
interleukin-2
- IS:
-
immunological synapse
- JNK:
-
c-Jun N-terminal kinase
- LFA1:
-
leukocyte function-associated antigen 1
- MHC:
-
major histocompatibility complex
- NIK:
-
NF-κB-inducing kinase
- PD-1:
-
programmed cell death protein 1
- PDK1:
-
phosphatidylinositol-dependent kinase 1
- PH:
-
pleckstrin homology
- PI3K:
-
phosphatidylinositol 3-kinase
- PIP2:
-
phosphatidylinositol 3,4-biphosphate
- PIP3:
-
phosphatidylinositol 3,4,5-triphosphate
- PKB:
-
protein kinase B
- PLCγ:
-
phospholipase C-γ1
- RHD:
-
Rel homology domain
- RING:
-
really interesting new gene
- SH:
-
Src homology
- SMAC:
-
supramolecular activation cluster
- TCR:
-
T cell receptor
- Th2:
-
T helper type 2
- TNF:
-
tumor necrosis factor
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Acknowledgements
This work was supported by the Swiss National Foundation, EU FP6, the International Association for Cancer Research (MLS) and the Deutsche Forschungsgemeinschaft (DK).
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Schmitz, M., Krappmann, D. Controlling NF-κB activation in T cells by costimulatory receptors. Cell Death Differ 13, 834–842 (2006). https://doi.org/10.1038/sj.cdd.4401845
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