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Divisions of
*
Tumor Biology,
Cell Biology, and
Cellular Biochemistry, Netherlands Cancer Institute, Amsterdam, The Netherlands
MHC class II molecules bind antigenic peptides in the late
endosomal/lysosomal MHC class II compartments (MIIC) before cell
surface presentation. The class II modulatory molecules HLA-DM and
HLA-DO mainly localize to the MIICs. Here we show that DM/DO complexes
continuously recycle between the plasma membrane and the lysosomal
MIICs. Like DM
and the class II-associated invariant chain, the
DO cytoplasmic tail contains potential lysosomal targeting signals.
The DO signals, however, are not essential for internalization of
the DM/DO complex from the plasma membrane or targeting to the MIICs.
Instead, the DO tail determines the distribution of both DM/DO and
class II within the multivesicular MIIC by preferentially localizing
them to the limiting membrane and, in lesser amounts, to the internal
membranes. This distribution augments the efficiency of class II
antigenic peptide loading by affecting the efficacy of lateral
interaction between DM/DO and class II molecules. Sorting of DM/DO and
class II molecules to specific localizations within the MIIC represents
a novel way of regulating MHC class II Ag
presentation.
This article has been cited by other articles:
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