Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells.
Trafficking of transmembrane receptors to a specific intracellular compartment is conducted by adaptor molecules that bind to target motifs within the cytoplasmic domains of cargo proteins. We generated mice containing a lymphoid-specific deficiency of AP-1 using RNAi knockdown technology. Inhibition of AP-1 expression in thymocytes blocks progression from double-positive immature thymocytes, resulting in complete absence of CD4(+) single-positive thymocytes and severe reduction of CD3(+)CD8(+) single-positive thymocytes. Analysis of the contribution of AP-1 deficiency on the interaction between mature CD4(+) T cells and antigen-presenting cells revealed that AP-1 is essential to efficient immune synapse formation and associated T cell activation, suggesting a possible mechanism of AP-1 function in thymocyte development.
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Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- T-Lymphocyte Subsets
- Reverse Transcriptase Polymerase Chain Reaction
- Receptors, Antigen, T-Cell
- RNA Interference
- Protein Subunits
- Ovalbumin
- Mice, Transgenic
- Mice, Knockout
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- T-Lymphocyte Subsets
- Reverse Transcriptase Polymerase Chain Reaction
- Receptors, Antigen, T-Cell
- RNA Interference
- Protein Subunits
- Ovalbumin
- Mice, Transgenic
- Mice, Knockout