Journal
CURRENT OPINION IN IMMUNOLOGY
Volume 31, Issue -, Pages 97-101Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.coi.2014.10.003
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Funding
- National Institute of Allergy and Infectious Diseases [1PO1AI076210-01A1]
- Manton Foundation
- Jeffrey Modell Foundation
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Engagement of the TCR/CD3 complex triggers a cascade of events that result in T lymphocyte activation and promote positive and negative selection of thymocytes, T lymphocyte migration and effector functions, development and activation of regulatory T cells. Gene mutations that abrogate early TCR signaling are associated with profound abnormalities of T lymphocyte development and function both in humans and in mice, causing susceptibility to severe infections since early in life. In recent years, a growing number of genetic defects have been discovered that reduce, but do not completely abrogate proximal TCR signaling. These defects result in complex phenotypic manifestations that are not limited to immunodeficiency, but also include immune dysregulation. The identification of these conditions may also prompt development of novel therapeutic strategies for autoimmune disorders.
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