Activation-induced polarized recycling targets T cell antigen receptors to the immunological synapse; involvement of SNARE complexes.
The mechanism by which T cell antigen receptors (TCR) accumulate at the immunological synapse has not been fully elucidated. Since TCRs are continuously internalized and recycled back to the cell surface, we investigated the role of polarized recycling in TCR targeting to the immunological synapse. We show here that the recycling endosomal compartment of T cells encountering activatory antigen-presenting cells (APCs) polarizes towards the T cell-APC contact site. Moreover, TCRs in transit through recycling endosomes are targeted to the immunological synapse. Inhibition of T cell polarity, constitutive TCR endocytosis, or recycling reduces TCR accumulation at the immunological synapse. Conversely, increasing the amount of TCRs in recycling endosomes before synapse formation enhanced their accumulation. Finally, we show that exocytic t-SNAREs from T cells cluster at the APC contact site and that tetanus toxin inhibits TCR accumulation at the immunological synapse, indicating that vesicle fusion mediated by SNARE complexes is involved in TCR targeting to the immunological synapse.
Das
Vincent
V
Unité de Biologie des Interactions Cellulaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée-2582, 75724 Paris Cedex 15, France.
Nal
Béatrice
B
Dujeancourt
Annick
A
Thoulouze
Maria-Isabel
MI
Galli
Thierry
T
Roux
Pascal
P
Dautry-Varsat
Alice
A
Alcover
Andrés
A
D000938:Antigen-Presenting Cells / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D050600:SNARE Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins