CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation.
J Exp Med
; 208(1): 149-65, 2011 Jan 17.
Article
em En
| MEDLINE
| ID: mdl-21220452
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Imunoglobulinas
/
Glicoproteínas de Membrana
/
Antígenos de Histocompatibilidade Classe II
/
Antígenos CD
/
Interleucina-10
/
Ubiquitina-Proteína Ligases
/
Antígeno B7-2
/
Ubiquitinação
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Austrália