| Dendritic cells (DCs) and B cells present antigen-derived peptides bound to major histocompatibility complex class II (MHC II) molecules for recognition by CD4-positive T lymphocytes. By regulating ubiquitination of the MHC II b chain, DCs control the intracellular traffic of peptide-MHC II complexes by targeting modified MHC II molecules to lysosomes. B lymphocytes also ubiquitinate their MHC II molecules, which remain at the plasma membrane. Here we report a striking difference in the length of the MHC II-conjugated ubiquitin (Ub) chains between DCs and B cells. Whereas MHC II molecules in immature DCs are modified by chains of 4-6 Ub, in B cells they are modified by 2-3 Ub. In DCs and B cells, increasing chain length led to increased MHC II endocytosis and sorting to late endosomes/lysosomes, while MHC II molecules containing only 1-2 Ub's did not reach late endosomes. Thus, the length of Ub chains plays a crucial role in controlling the intracellular fate of MHC II molecules in DCs and B cells. |
