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.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Diana A
DA
Alvarez Arias
Nami
N
McCarty
Linrong
L
Lu
Roberto A
RA
Maldonado
Mari L
ML
Shinohara
Harvey
H
Cantor
D033961:Adaptor Protein Complex 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015151:Immunoblotting; D054992:Immunological Synapses / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D033961:Adaptor Protein Complex 1; D006649:Histocompatibility Antigens; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin