MHC class II distribution in dendritic cells and B cells is determined by ubiquitin chain length

Dendritic cells (DCs) and B cells present antigen-derived peptides bound to MHC class II (MHC II) molecules for recognition by CD4-positive T lymphocytes. DCs control the intracellular traffic of peptide-MHC II complexes by regulating the ubiquitination of MHC II. In resting or "immature"...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-06, Vol.109 (23), p.8820-8827
Main Authors: Ma, Jessica K., Platt, Mia Y., Eastham-Anderson, Jeffrey, Shin, Jeoung-Sook, Mellman, Ira
Format: Article
Language:English
Subjects:
Adaptor Proteins, Vesicular Transport - metabolism
Animals
Antibodies
Antigens
Antigens - immunology
Antigens - metabolism
B lymphocytes
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Biological Sciences
Blasts
Blotting, Western
Bone marrow cells
CD4-Positive T-Lymphocytes - immunology
Cell Line
Cell membranes
Cells
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Endocytosis
Endocytosis - physiology
Flow Cytometry
Genes, MHC Class II - genetics
Immunoprecipitation
Internalization
Lymphocytes
Mice
Molecules
Multiprotein Complexes - genetics
Multiprotein Complexes - immunology
Multiprotein Complexes - metabolism
Peptides
Recombinant Fusion Proteins - metabolism
T lymphocytes
Ubiquitin - metabolism
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Summary:Dendritic cells (DCs) and B cells present antigen-derived peptides bound to MHC class II (MHC II) molecules for recognition by CD4-positive T lymphocytes. DCs control the intracellular traffic of peptide-MHC II complexes by regulating the ubiquitination of MHC II. In resting or "immature" DCs, ubiquitinated MHC II molecules are targeted to lysosomes, but upon pathogen-induced "maturation," ubiquitination is down-regulated and MHC II can accumulate on the plasma membrane of mature DCs. Although B cells constitutively ubiquitinate their MHC II, it unexpectedly remains at the surface. We find that DCs and B cells differ in MHC ll-conjugated ubiquitin (Ub) chain length: four to six Ub in immature DCs vs. two to three in B cells. In both cell types, experimentally increasing Ub chain length led to efficient lysosomal transport of MHC II, whereas MHC II with fewer than two Ubs did not reach lysosomes. Thus, Ub chain length plays a crucial role in regulating the intracellular fate and function of MHC II in DCs and B cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1202977109