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Costimulatory ligand CD70 is delivered to the immunological synapse by shared intracellular trafficking with MHC class II molecules
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, 104(14), 5989-5994. National Academy of Sciences
- Publication Year :
- 2007
- Publisher :
- Proceedings of the National Academy of Sciences, 2007.
-
Abstract
- 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 II compartments (MIIC). In cells lacking the machinery for antigen presentation by MHC class II, CD70 travels by default to the plasma membrane. Introduction of class II transactivator sufficed to reroute CD70 to MIIC. Vesicular trafficking of CD70 and MHC class II 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.
- Subjects :
- Lipopolysaccharides
T cell
Genetic Vectors
Antigen presentation
Antigen-Presenting Cells
Bone Marrow Cells
Ligands
Lymphocyte Activation
Immunological synapse
Cell membrane
Mice
medicine
Animals
Humans
Fluorescent Antibody Technique, Indirect
Antigen-presenting cell
Melanoma
Cells, Cultured
MHC class II
Multidisciplinary
biology
Cell Membrane
Gene Transfer Techniques
Histocompatibility Antigens Class II
Dendritic Cells
Biological Sciences
Coculture Techniques
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Endocytic vesicle
Microscopy, Fluorescence
biology.protein
Memory T cell
CD27 Ligand
HeLa Cells
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 104
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....9da597e9fb621ad6587dd97e0897e3d3