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Hsp90 associates with N‐terminal extended peptides and is required for direct antigen presentation
Author(s) -
Garg Manish,
Callahan Margaret K,
Srivastava Pramod K
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1067.19
Subject(s) - mhc class i , epitope , antigen presentation , hsp90 , lactacystin , antigen , major histocompatibility complex , t cell , chemistry , antigen processing , chaperone (clinical) , microbiology and biotechnology , endoplasmic reticulum , cytosol , peptide , cytotoxic t cell , proteasome , biochemistry , heat shock protein , biology , proteasome inhibitor , immune system , immunology , in vitro , enzyme , medicine , pathology , gene
Antigen presentation by MHC I molecules requires the generation of peptides in the cytosol, ferrying of peptides from cytosol to endoplasmic reticulum, loading of MHC I with peptides, and transport of MHC I‐peptide complexes to the cell surface. Hsp90 is a cytosolic chaperone known to associate with peptide and peptide precursors of MHC I epitopes. We report here that treatment of a variety of cells with hsp90 inhibitors leads to generation of “empty” MHC I molecules on the cell surface, due to inhibited loading of MHC I with peptides. Inhibition of hsp90 does not inhibit protein synthesis in general, nor synthesis of MHC I in particular, nor does it affect the activity of proteasomes. Hsp90‐inhibited cells, like lactacystin‐treated cells, are poor stimulators of T lymphocytes. The role of hsp90 in presentation of an ovalbumin epitope is shown to be at a post‐proteasomal step: hsp90 associates with N‐terminally extended precursors of the SIINFEKL epitope, and such peptides are depleted from hsp90 preparations in inhibitor‐treated cells. These results argue for a substantial role for hsp90 in chaperoning of antigenic peptides in direct presentation. This work was supported by NIH grant CA 084479 to P.K.S.