Cutting edge: HLA-DO impairs the incorporation of HLA-DM into exosomes.

In multivesicular bodies, HLA-DM (DM) assists the loading of antigenic peptides on classical MHC class II molecules such as HLA-DR. In cells expressing HLA-DO (DO), DM is redistributed from the internal vesicles to the limiting membrane of these organelles. This suggests that DO might reduce DM incorporation into exosomes, which are shed upon fusion of multivesicular bodies with the plasma membrane.

Forced expression of HLA-DM at the surface of dendritic cells increases loading of synthetic peptides on MHC class II molecules and modulates T cell responses.

Adoptive transfer of autologous dendritic cells (DCs) loaded with tumor-associated CD4 and CD8 T cell epitopes represents a promising avenue for the immunotherapy of cancer. In an effort to increase the loading of therapeutic synthetic peptides on MHC II molecules, we used a mutant of HLA-DM (DMY) devoid of its lysosomal sorting motif and that accumulates at the cell surface. Transfection of DMY into HLA-DR(+) cells resulted in increased loading of the exogenously supplied HA(307-318) peptide, as well as increased stimulation of HA-specific T cells.

Sorting of MHC class II molecules into exosomes through a ubiquitin-independent pathway.

Major histocompatibility complex class II (MHC-II) molecules accumulate in exocytic vesicles, called exosomes, which are secreted by antigen presenting cells. These vesicles are released following the fusion of multivesicular bodies (MVBs) with the plasma membrane. The molecular mechanisms regulating cargo selection remain to be fully characterized.

Novel antibody specificities targeting glycoprotein B of cytomegalovirus identified by molecular library technology.

Antibodies provide some protection against cytomegalovirus-mediated disease. All aspects of antibody recognition of important viral antigens are, however, not fully appreciated. Glycoprotein B (gB), a key protein in the viral membrane, participates in viral infection and it is a component of prototype vaccines.