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

• DOI: 10.1084/jem.20092203
• Publication Date: 2011-01-11T04:07:09Z
• Authors: Lina E. Tze; Keisuke Horikawa; Heather Domaschenz; Debbie R. Howard; Carla M. Roots; Robert J. Rigby; David A. Way; Mari Ohmura-Hoshino; Satoshi Ishido; Christopher E. An...; Mariapia A. Degli...; Christopher C. Go...
• Keywords: Male; den; 570; Ubiquitin-Protein Ligases; animal experiment; Molecular Sequence Data; major histocompatibility antigen class 2; Immunoglobulins; animal cell; CD86 antigen; Article; ethylnitrosourea; Mice; 03 medical and health sciences; 0302 clinical medicine; Antigens, CD; vaccine; Keywords: CD83 antigen; Animals; Humans; controlled study; Amino Acid Sequence; degradation; Membrane Glycoproteins; Base Sequence; Cell Membrane; article; Histocompatibility Antigens Class II; Ubiquitination; Dendritic Cells; Interleukin-10; 3. Good health; ubiquitin protein ligase; HEK293 Cells; CD83 Antigen; cytokine production; antigen expression; B7-2 Antigen; interleukin 10; Sequence Alignment

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.