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Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2556-61. doi: 10.1073/pnas.0913671107. Epub 2010 Jan 25.

Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells.

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  • 1Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.


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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