Ovalbumin-derived precursor peptides are transferred sequentially from gp96 and calreticulin to MHC class I in the endoplasmic reticulum.
Cellular peptides generated by proteasomal degradation of proteins in the cytosol and destined for presentation by MHC class I (MHC-I) are associated with several chaperones. Heat shock proteins 70, 90, and the TCP-1 ring complex have been implicated as important cytosolic players for chaperoning these peptides. In this study, we report that gp96 and calreticulin are essential for chaperoning peptides in the endoplasmic reticulum. Importantly, we demonstrate that cellular peptides are transferred sequentially from gp96 to calreticulin and then to MHC-I forming a relay line. Disruption of this relay line by removal of gp96 or calreticulin prevents the binding of peptides by MHC-I and hence presentation of the MHC-I-peptide complex on the cell surface. Our results are important for understanding how peptides are processed and trafficked within the endoplasmic reticulum before exiting in association with MHC-I H chains and beta2-microglobulin as a trimolecular complex.
Kropp
Laura E
LE
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Garg
Manish
M
Binder
Robert J
RJ
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D037282:Calreticulin / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D010047:Ovalbumin / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D021381:Protein Transport / Q000276:immunology; D001613:beta 2-Microglobulin / Q000378:metabolism
D037282:Calreticulin; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D010455:Peptides; D011498:Protein Precursors; D001613:beta 2-Microglobulin; C053387:endoplasmin; D010047:Ovalbumin
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