Journal
TRENDS IN IMMUNOLOGY
Volume 28, Issue 3, Pages 124-131Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.it.2007.01.004
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Funding
- NATIONAL CANCER INSTITUTE [P01CA109901] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI045846, R01AI047281] Funding Source: NIH RePORTER
- NCI NIH HHS [P01 CA 109901] Funding Source: Medline
- NIAID NIH HHS [R01 AI 47281, R01 AI 45846] Funding Source: Medline
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At two checkpoints, T cell development is controlled by T cell receptor (TCR) signaling, which determines survival and lineage commitment. At the first of these checkpoints, signaling by the pre-TCR, the gamma delta TCR or the alpha beta TCR has a major but nonexclusive impact on whether cells will become CD4(-)CD8(-) gamma delta or CD4(+)CD8(+) alpha beta lineage cells. Pre-TCR signals synergize with moderate Notch signals to generate up lineage cells. Relatively strong signals by the gamma delta TCR (or early expressed alpha beta TCR) in the absence of Notch signaling are sufficient to yield gamma delta lineage cells. However, relatively weak signals of the latter two receptors combined with strong Notch signaling result in the formation of alpha beta lineage cells that generate a diverse alpha beta TCR repertoire in pre-TCR-deficient mice. It remains to be determined whether TCR and/or Notch signals instruct or confirm predetermined lineage fate.
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