title: Ovalbumin-derived precursor peptides are transferred sequentially from gp96 and calreticulin to MHC class I in the endoplasmic reticulum.
abstract: 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.
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Kropp
authors.forename: Manish
authors.initials: M
authors.lastname: Garg
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Binder
mesh_terms: 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
chemical_list: 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
references.citation: J Immunol. 2007 Dec 1;179(11):7254-61
references.pmid: 18025167
references.citation: Immunol Rev. 2005 Oct;207:89-99
references.pmid: 16181329
references.citation: Immunity. 2009 Jan 16;30(1):21-32
references.pmid: 19119025
references.citation: Eur J Immunol. 1997 Sep;27(9):2441-9
references.pmid: 9341791
references.citation: Mol Cell. 2003 Sep;12(3):565-76
references.pmid: 14527404
references.citation: J Exp Med. 1999 Mar 1;189(5):797-802
references.pmid: 10049943
references.citation: Nature. 2002 Oct 3;419(6906):480-3
references.pmid: 12368856
references.citation: Nat Immunol. 2002 Dec;3(12):1177-84
references.pmid: 12436110
references.citation: J Exp Med. 1997 Aug 4;186(3):461-6
references.pmid: 9236199
references.citation: J Biol Chem. 2002 Aug 16;277(33):29686-97
references.pmid: 12052826
references.citation: EMBO J. 1993 Aug;12(8):3143-51
references.pmid: 8344253
references.citation: Nat Cell Biol. 2001 Oct;3(10):891-6
references.pmid: 11584270
references.citation: Science. 1989 Jun 2;244(4908):1072-5
references.pmid: 2471266
references.citation: J Immunol. 1999 Feb 1;162(3):1303-9
references.pmid: 9973383
references.citation: Immunogenetics. 1994;39(2):93-8
references.pmid: 8276462
references.citation: Eur J Immunol. 1997 Jan;27(1):336-41
references.pmid: 9022037
references.citation: Cell. 1996 Jul 26;86(2):253-62
references.pmid: 8706130
references.citation: Immunity. 1994 Sep;1(6):479-89
references.pmid: 7534616
references.citation: J Immunol. 1999 Jun 1;162(11):6426-32
references.pmid: 10352256
references.citation: Proc Natl Acad Sci U S A. 1986 May;83(10):3407-11
references.pmid: 3458189
references.citation: J Immunol. 1996 Sep 1;157(5):1823-6
references.pmid: 8757297
references.citation: Nat Immunol. 2004 Jul;5(7):678-84
references.pmid: 15224093
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1662-7
references.pmid: 18216248
references.citation: J Exp Med. 1994 Jan 1;179(1):335-40
references.pmid: 8270878
references.citation: Nat Rev Immunol. 2003 Dec;3(12):952-61
references.pmid: 14647477
references.citation: Microbiol Immunol. 2008 Feb;52(2):94-106
references.pmid: 18380807
references.citation: J Biol Chem. 2001 May 18;276(20):17163-71
references.pmid: 11278929
references.citation: Immunity. 2001 Jul;15(1):95-104
references.pmid: 11485741
references.citation: J Exp Med. 1994 Nov 1;180(5):1591-7
references.pmid: 7964447
references.citation: Curr Opin Cell Biol. 2008 Dec;20(6):624-31
references.pmid: 18926908
references.citation: Biochem Biophys Res Commun. 1999 Sep 7;262(3):813-8
references.pmid: 10471407
references.citation: Eur J Immunol. 1997 Jul;27(7):1685-90
references.pmid: 9247578
references.citation: Eur J Immunol. 1999 Jun;29(6):1858-70
references.pmid: 10382748
references.citation: Immunity. 2006 May;24(5):523-34
references.pmid: 16713971
references.citation: J Immunol. 2000 Nov 15;165(10):5656-63
references.pmid: 11067922
references.citation: Nat Rev Immunol. 2002 Mar;2(3):185-94
references.pmid: 11913069
references.citation: J Exp Med. 1995 Sep 1;182(3):885-9
references.pmid: 7650492