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/ß, Enhances the Presentation of an Immunodominant Lymphocytic Choriomeningitis Virus T Cell Epitope1
*
Research Department, Cantonal Hospital St. Gall, St. Gallen, Switzerland;
Institute of Experimental Immunology, Department of Pathology, University Hospital Zürich, Zürich, Switzerland;
Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and
§
Institute for Biochemistry, Medical Faculty (Charité), Humboldt University, Berlin, Germany
The proteasome is a large protease complex that generates most of
the peptide ligands of MHC class I molecules either in their final form
or in the form of N-terminally extended precursors. Upon the
stimulation of cells with IFN-
, three constitutively expressed
subunits of the 20S proteasome are replaced by the inducible subunits
LMP2 (low-molecular mass polypeptide 2), LMP7, and MECL-1
(multicatalytic endopeptidase complex-like-1) to form so-called
immunoproteasomes. We show in this study that overexpression of these
three subunits in triple transfectants led to a marked enhancement in
the H-2Ld-restricted presentation of the immunodominant
nonameric epitope NP118, which is derived from the nucleoprotein (NP)
of lymphocytic choriomeningitis virus. Overexpression of the 
and
ß subunits of the IFN--inducible proteasome regulator PA28, in
contrast, did not have a comparable effect. In vitro, immunoproteasomes
as compared with constitutive proteasomes generated higher amounts of
11- and 12-mer fragments containing the NP118 epitope. These are likely
to be cytosolic precursors of NP118, as a proline anchor residue in the
second position of NP118 may interfere with TAP-mediated transport of
the nonameric epitope itself. In conclusion, we provide evidence that
up-regulation of the three inducible subunits, LMP2, LMP7, and MECL-1,
can result in a marked improvement of Ag presentation and that,
depending on the epitope, PA28 and immunoproteasomes may differentially
affect Ag processing.
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|
|
|
|
|
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