Regulation of MHC class II surface expression in dendritic cells by ubiquitination

Abstract

Dendritic cells (DC) are antigen presenting cells specialized in antigen uptake, processing and presentation. Maturation of DC is an essential process in order to activate T cells in the lymph nodes and is characterized by upregulation of MHCII on the cell surface. Antigen presentation via MHCII is of great importance in the immune system and is a central process in adaptive immunity. In immature DC most of the newly formed peptide-MHCII (pMHCII) complexes are rapidly ubiquitinated, either directly or after expression on the plasma membrane, driving the active sorting of pMHCII to intraluminal vesicles at multivesicular bodies. MHCII synthesis is temporarily enhanced in maturing DC and ubiquitination of MHCII is simultaneously prevented, resulting in a high expression of stable MHCII loaded with antigenic peptides. The process and regulation of MHCII ubiquitination is, however, incompletely understood. Recent insights have been provided by discovery of the role of MARCH ligases and ITAM signaling in regulating ubiquitination. By understanding MHCII regulation it might be possible to modulate antigen presentation, preferably in specific subsets of DC. Stimulating the presentation of tumor-antigens on MHCII could improve cancer treatment in patients and might result in ‘tumor memory’. Furthermore, in all other diseases and infections where the adaptive immune system is involved, understanding the regulation of MHCII expression and antigen presentation will be of great value.