Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 14, Pages 5989-5994Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0700946104
Keywords
costimulation; dendritic cell; intracellular transport
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TNF family member CD70 is the ligand of CD27, a costimulatory receptor that shapes effector and memory T cell pools. Tight control of CD70 expression is required to prevent lethal immunodeficiency. By selective transcription, CD70 is largely confined to activated lymphocytes and dendritic cells (DC). We show here that, in addition, specific intracellular routing controls its plasma membrane deposition. In professional antigen-presenting cells, such as DC, CD70 is sorted to late endocytic vesicles, defined as MHC class 11 compartments (MIIC). In cells lacking the machinery for antigen presentation by MHCclass II, CD70 travels by default to the plasma membrane. Introduction of class 11 transactivator sufficed to reroute CD70 to MIIC. Vesicular trafficking of CD70 and MHC class 11 is coordinately regulated by the microtubule-associated dynein motor complex. We show that when maturing DC make contact with T cells in a cognate fashion, newly synthesized CD70 is specifically delivered via MIIC to the immunological synapse. Therefore, we propose that routing of CD70 to MIIC serves to coordinate delivery of the T cell costimulatory signal in time and space with antigen recognition.
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