In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-02-11)
Abstract:
T cells defend our body against cancer and infectious agents such as viruses. However, they can also cause rheumatoid arthritis and other autoimmune diseases by attacking healthy tissue. T cells recognize target cells via receptor proteins on their surface. To maximize the variety of infections and cancers our immune system can recognize, we generate millions of T cells with different T cell receptors every day. To ensure T cells work correctly, T cell receptors are tested at various checkpoints. The first checkpoint involves a process called beta (β) selection, during which T cells produce their first T cell receptor – the so-called pre-T cell receptor. This receptor causes T cells to divide and mature, and sets their future identity or “fate”. To complete β-selection, T cells must also receive signals from another surface receptor – one that belongs to the Notch family, which determines cell fate in many different tissues. The Notch receptor and the pre-T cell receptor both activate an enzyme called PI3K – a key mediator of β-selection. But the pre-T cell receptor also activates another enzyme called Itpkb that is required for T cell development. Westernberg, Conche et al. have now investigated how these different proteins and signaling processes work and interact during β-selection, using mice that lack several immune genes, including the gene that produces Itpkb. The results of the experiments show that during β-selection, Itpkb limits the ability of PI3K to activate some of its key target proteins. This “dampened” PI3K signaling ensures that both the pre-T cell receptor and the Notch receptor must be activated to trigger T cell maturation. Without Itpkb, β-selection can occur in the absence of Notch signaling. As Notch signaling is important for determining the fate of many different cell types, Westernberg, Conche et al.’s findings raise the possibility that Itpkb might also regulate cell fate determination in other tissues. Moreover, Itpkb may suppress tumor development, because excessive PI3K signaling drives many cancers.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.10786.001
DOI:
10.7554/eLife.10786.002
DOI:
10.7554/eLife.10786.003
DOI:
10.7554/eLife.10786.004
DOI:
10.7554/eLife.10786.005
DOI:
10.7554/eLife.10786.006
DOI:
10.7554/eLife.10786.007
DOI:
10.7554/eLife.10786.008
DOI:
10.7554/eLife.10786.009
DOI:
10.7554/eLife.10786.010
DOI:
10.7554/eLife.10786.011
DOI:
10.7554/eLife.10786.012
DOI:
10.7554/eLife.10786.013
DOI:
10.7554/eLife.10786.014
DOI:
10.7554/eLife.10786.015
DOI:
10.7554/eLife.10786.016
DOI:
10.7554/eLife.10786.017
DOI:
10.7554/eLife.10786.018
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
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