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Essential role of LAT in T cell development
W Zhang1, C L Sommers, D N Burshtyn
1Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Immunity
|April 16, 1999
Summary
Linker molecule LAT is crucial for T cell development and activation. LAT deficiency blocks T cell maturation in mice, highlighting its essential role in the immune system.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The linker molecule LAT is activated by tyrosine kinases upon T cell receptor (TCR) engagement.
- Phosphorylated LAT serves as a scaffold, binding numerous critical signaling molecules.
- Previous studies using LAT-deficient cell lines indicated its central role in TCR-mediated signaling.
Purpose of the Study:
- To investigate the role of LAT in T cell development and activation.
- To understand the function of LAT in the adaptive immune response.
Main Methods:
- Gene targeting was employed to disrupt the LAT gene in mice.
- Flow cytometric analysis was used to assess T cell populations and development.
- Functional assays were performed on NK cells and platelets.
Main Results:
- LAT-deficient mice appeared healthy with normal B cell populations.
- A complete absence of mature peripheral T cells was observed in LAT-deficient mice.
- Intrathymic T cell development was arrested at the CD4- CD8- stage.
- No significant abnormalities in NK cell or platelet function were detected.
Conclusions:
- LAT is essential for both T cell activation and T cell development.
- Disruption of LAT severely impairs T cell maturation, leading to a lack of peripheral T cells.
- LAT plays a critical, non-redundant role in adaptive immunity.