CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation

Effective vaccine adjuvants must induce expression of major histocompatibility (MHC) class II proteins and the costimulatory molecule CD86 on dendritic cells (DCs). However, some adjuvants elicit production of cytokines resulting in adverse inflammatory consequences. Development of agents that selec...

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Bibliographic Details
Published in:The Journal of experimental medicine 2011-01, Vol.208 (1), p.149-165
Main Authors: Tze, Lina E, Horikawa, Keisuke, Domaschenz, Heather, Howard, Debbie R, Roots, Carla M, Rigby, Robert J, Way, David A, Ohmura-Hoshino, Mari, Ishido, Satoshi, Andoniou, Christopher E, Degli-Esposti, Mariapia A, Goodnow, Christopher C
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antigens, CD - chemistry
Antigens, CD - genetics
Antigens, CD - immunology
B7-2 Antigen - immunology
Base Sequence
CD83 Antigen
Cell Membrane - immunology
Dendritic Cells - immunology
HEK293 Cells
Histocompatibility Antigens Class II - immunology
Humans
Immunoglobulins - chemistry
Immunoglobulins - genetics
Immunoglobulins - immunology
Interleukin-10 - immunology
Male
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - genetics
Membrane Glycoproteins - immunology
Mice
Molecular Sequence Data
Sequence Alignment
Ubiquitin-Protein Ligases - immunology
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
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Summary:Effective vaccine adjuvants must induce expression of major histocompatibility (MHC) class II proteins and the costimulatory molecule CD86 on dendritic cells (DCs). However, some adjuvants elicit production of cytokines resulting in adverse inflammatory consequences. Development of agents that selectively increase MHC class II and CD86 expression without triggering unwanted cytokine production requires a better understanding of the molecular mechanisms influencing the production and degradation of MHC class II and CD86 in DCs. Here, we investigate how CD83, an immunoglobulin protein expressed on the surface of mature DCs, promotes MHC class II and CD86 expression. Using mice with an N-ethyl-N-nitrosourea-induced mutation eliminating the transmembrane (TM) region of CD83, we found that the TM domain of CD83 enhances MHC class II and CD86 expression by blocking MHC class II association with the ubiquitin ligase MARCH1. The TM region of CD83 blocks interleukin 10-driven, MARCH1-dependent ubiquitination and degradation of MHC class II and CD86 in DCs. Exploiting this posttranslational pathway for boosting MHC class II and CD86 expression on DCs may provide an opportunity to enhance the immunogenicity of vaccines.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20092203