THE MHC CLASS-II MOLECULE H2-M IS TARGETED TO AN ENDOSOMAL COMPARTMENT BY A TYROSINE-BASED TARGETING MOTIF

The nonpolymorphic human class II molecule HLA-DM (DM) has been found to play a key role in antigen presentation by MHC class II molecules, HLA-DM and its murine equivalent H2-M are located intracellularly and are absent from the cell surface, In transfected HeLa cells, H2-M was transported to an endosomal compartment in the absence of invariant ch ain, A tyrosine-based targeting motif in the cytoplasmic tail of HP-M beta was responsible for the endosomal location and, if this tyrosine was mutated, H2-M accumulated at the cell surface. In the presence of invariant chain the mutated H2-M was redistributed to endosomes. The t argeting motif of H2-M appeared not to be crucial for efficient peptid e loading of class II, but if the invariant chain targeting motif also was removed, peptide loading decreased drastically. Thus, the targeti ng motif of H2-M appears to be supplementary, rather than essential fo r class II-peptide association.