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Heat-Shock Protein 90 Associates With N-Terminal Extended Peptides And Is Required For Direct And Indirect Antigen Presentation, Margaret K. Callahan, Manish Garg, Pramod K. Srivastava

UCHC Articles - Research

CD8⁺ T cells recognize peptide fragments of endogenously synthesized antigens of cancers or viruses, presented by MHC I molecules. Such antigen presentation requires the generation of peptides in the cytosol, their passage to the endoplasmic reticulum, loading of MHC I with peptides, and transport of MHC I–peptide complexes to the cell surface. Heat-shock protein (hsp) 90 is a cytosolic chaperone known to associate with peptide and peptide precursors of MHC I epitopes. We report here that treatment of cells with hsp90 inhibitors leads to generation of “empty” MHC I caused by inhibited loading of MHC I with peptides. Inhibition …