Hudson Laboratory Research Areas
We found that class I MHC stability was indeed decreased in HHV-7-infected T cells, and that a 55 kDa viral glycoprotein co-immunoprecipitated with class I MHC molecules. We identified this associated protein as the product of the HHV-7 U21 open reading frame. U21 binds to newly synthesized, properly folded MHC class I molecules in the ER, shortly after synthesis. Expression of U21 in cultured cells results in a reduction of class I molecules on the plasma membrane and a dramatic redistribution of class I molecules to lysosomes.
Targeting of a protein to the lysosomal compartment is generally accomplished through association of cellular sorting machinery with a sorting motif contained within its cytoplasmic tail. Surprisingly, however, even expression of a tailless U21 can divert class I MHC molecules to lysosomes. Thus, it is the lumenal domain of U21 that is responsible for diverting class I molecules to lysosomes.
How does the lumenal domain of U21 divert class I MHC molecules, and what is the cellular mechanism for lysosomal sorting that U21 harnesses for its benefit? We focus on characterizing this novel immunoevasive strategy as a means of dissecting the underlying cell biology behind this lysosomal sorting mechanism.