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Our
cell-based tumor vaccines rely on the surface expression
of MHC class II molecules on the surface of the vaccine cell
to stimulate CD4+ T cells. I am studying the role that membrane
microdomains serve in concentrating MHC II on the cell surface.
The microdomains, termed lipid rafts, act as a platform to
anchor certain membrane proteins, including MHC II. When
lipid rafts are disrupted by cholesterol sequestering compounds,
antigen presentation by vaccine cells is significantly decreased.
We are trying to determine if MHC II molecules associate
with the raft prior to any T-cell interaction or if they
translocate into the raft after T-cell stimulation. Additionally,
we are examining the role of the cytoplasmic tail of MHC
II and its role in lipid raft mediated antigen presentation.
Early results indicate that the cholesterol sequestering
drugs do not effect antigen presentation and suggest that
class II molecules lacking a cytoplasmic are not found in
the lipid rafts. |
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