By opposing IL-10–driven, MARCH1-mediated ubiquitination and degradation of MHC class II, CD83 may boost the immunogenicity of dendritic cells

Abramoff

Aerts-Toegaert

Andoniou

Bartee

Carla M. Roots

Cella

Chan

Chang

Christopher C. Goodnow

Christopher E. Andoniou

Coscoy

Cosgrove

Couper

Cramer

David A. Way

De Gassart

de Waal Malefyt

Debbie R. Howard

Fujimoto

García-Martínez

Goto

Heather Domaschenz

Hewitt

Hijikata

Horikawa

Ishido

Ishii

Jayawardane

Jenkins

Keisuke Horikawa

Kitamura

Klein

Koppelman

Kretschmer

Kropshofer

Kruse

Kuwano

Lechmann

Lenz

Lina E. Tze

Longhi

Mari Ohmura-Hoshino

Mariapia A. Degli-Esposti

Mata-Haro

Matsuki

McKee

McKinsey

Ohmura-Hoshino

Pashine

Prazma

Prechtel

Redpath

Reed

Riberdy

Robert J. Rigby

Rode

Sanchez

Satoshi Ishido

Shin

Slobedman

Spencer

Steinman

Thibodeau

Unternaehrer

van Niel

Villadangos

Vinuesa

Willems

Young

Zhou

Zilber

Zinser

The Journal of Experimental Medicine

English

PubMed

Effective vaccine adjuvants must induce expression of major histocompatability (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

Tze, Lina

Horikawa, Keisuke

Domaschenz, Heather

Howard, Debbie

Roots, Carla

Rigby, Robert

Way, David

Ohmura-Hoshino, Maria

Ishido, Satoshi

Andoniou, Christopher E

Degli-Esposti, Mariapia A

Goodnow, Christopher

The Australian National University

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 histocompatability (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.</jats:p

Crossref

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

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3023131

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

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