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.