title: Expression of major histocompatibility complex class I proteins and their antigen processing chaperones in mouse embryonic stem cells from fertilized and parthenogenetic embryos.
abstract: Embryonic stem (ES) cells are pluripotent cells with the potential to differentiate into cells or tissues that may be used for transplantation therapy. Parthenogenetic ES (pES) cells have been recently derived from both mouse and human oocytes and hold promise as a cell source that is histocompatible to the oocyte donor. Because of the importance of major histocompatibility complex (MHC) antigens in mediating tissue rejection or acceptance, we examined levels of mRNA and protein expression of MHC class I proteins, as well as several MHC class I antigen processing and presentation chaperones in mouse ES cells derived from both fertilized (fES) and parthenogenetic (pES) embryos. We found that H-2K, Qa-2, TAP1, TAP2, and tapasin mRNAs were all expressed at low levels in undifferentiated and differentiating ES cells and were significantly upregulated in response to interferon-gamma (IFN-gamma) treatment following 14 days of differentiation. Likewise, expression of H-2K(b) and H-2K(k) proteins were upregulated to detectable levels by IFN-gamma after 14 days of differentiation, but Qa-2 protein expression remained low or absent. We also found that MHC class I, TAP1, TAP2, and tapasin mRNAs were all expressed at very low levels in ES cells compared with T cells, suggesting transcriptional regulation of these genes in ES cells. Calnexin, a chaperone molecule involved in other pathways than MHC expression, had mRNA levels that were similar in ES cells and T cells and was not upregulated by IFN-gamma in ES cells. Overall, ES cells derived from fertilized embryos and parthenogenetic embryos displayed remarkably similar patterns of gene expression at the mRNA and protein levels. The similarity between the fES and pES cell lines with regard to expression of MHC class I and antigen-processing machinery provides evidence for the potential usefulness of pES cells in transplantation therapy.
authors.affiliation: Department of Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Lampton
authors.forename: R J
authors.initials: RJ
authors.lastname: Crooker
authors.forename: J A
authors.initials: JA
authors.lastname: Newmark
authors.forename: C M
authors.initials: CM
authors.lastname: Warner
mesh_terms: D000818:Animals; D037281:Calnexin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000096:biosynthesis*; D010312:Parthenogenesis; D012333:RNA, Messenger / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; C107762:tapasin; D037281:Calnexin; D007371:Interferon-gamma
references.citation: Stem Cells. 2004;22(4):448-56
references.pmid: 15277692
references.citation: Biol Reprod. 1998 Oct;59(4):941-52
references.pmid: 9746747
references.citation: Curr Biol. 2000 Aug 24;10(16):989-92
references.pmid: 10985386
references.citation: Stem Cells. 2006 Oct;24(10):2192-201
references.pmid: 16794265
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19081-6
references.pmid: 16357205
references.citation: Cloning Stem Cells. 2008 Mar;10(1):11-24
references.pmid: 18092905
references.citation: Nature. 2004 Apr 22;428(6985):860-4
references.pmid: 15103378
references.citation: Cancer Res. 2001 Feb 1;61(3):1095-9
references.pmid: 11221838
references.citation: Nucleic Acids Res. 2003 Dec 15;31(24):e154
references.pmid: 14654707
references.citation: Immunol Rev. 1997 Feb;155:29-40
references.pmid: 9059880
references.citation: Biol Reprod. 1994 Aug;51(2):169-83
references.pmid: 7948472
references.citation: J Neurosci. 2005 May 11;25(19):4694-705
references.pmid: 15888645
references.citation: Nat Immunol. 2000 Sep;1(3):234-8
references.pmid: 10973281
references.citation: J Cell Sci. 2006 Feb 15;119(Pt 4):615-23
references.pmid: 16467570
references.citation: Stem Cells. 2008 Aug;26(8):1939-50
references.pmid: 18535153
references.citation: Biol Reprod. 1987 Apr;36(3):611-6
references.pmid: 3593833
references.citation: J Reprod Immunol. 2000 Feb;46(1):1-15
references.pmid: 10708239
references.citation: Nature. 2006 Jan 12;439(7073):216-9
references.pmid: 16227970
references.citation: Science. 1998 Nov 6;282(5391):1145-7
references.pmid: 9804556
references.citation: Cloning Stem Cells. 2007 Fall;9(3):291-2
references.pmid: 17907939
references.citation: Cell. 1992 Dec 24;71(7):1205-14
references.pmid: 1473153
references.citation: J Reprod Immunol. 2008 Jun;78(1):28-39
references.pmid: 18061684
references.citation: J Immunol. 1993 Apr 1;150(7):2805-13
references.pmid: 8454857
references.citation: Biol Reprod. 1997 Sep;57(3):561-8
references.pmid: 9282991
references.citation: Science. 2007 Jan 26;315(5811):482-6
references.pmid: 17170255
references.citation: Immunol Lett. 2002 Oct 1;83(3):197-207
references.pmid: 12095710
references.citation: J Immunol. 2007 Mar 15;178(6):3390-9
references.pmid: 17339433
references.citation: Stem Cells Dev. 2006 Oct;15(5):707-17
references.pmid: 17105406
references.citation: J Immunol. 2002 Mar 1;168(5):2200-11
references.pmid: 11859106
references.citation: Stem Cells. 2006 Feb;24(2):221-9
references.pmid: 16109762
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9864-9
references.pmid: 12114532
references.citation: Reprod Fertil Dev. 2004;16(7):729-41
references.pmid: 15740696
references.citation: J Exp Med. 1971 Jul 1;134(1):83-102
references.pmid: 4397663
references.citation: Cell Res. 2007 Sep;17(9):792-803
references.pmid: 17768400
references.citation: Lancet. 2005 Dec 10;366(9502):2019-25
references.pmid: 16338451
references.citation: Ann N Y Acad Sci. 2007 Jun;1106:209-18
references.pmid: 17360798
references.citation: Biotechniques. 2002 Jun;32(6):1372-4, 1376, 1378-9
references.pmid: 12074169
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Hum Immunol. 2007 Jan;68(1):1-11
references.pmid: 17207707
references.citation: Nature. 2008 May 15;453(7193):322-9
references.pmid: 18480813
references.citation: Development. 1994 Jun;120(6):1473-82
references.pmid: 8050357
references.citation: Cell Biol Int. 2007 Sep;31(9):1072-8
references.pmid: 17459733
references.citation: J Immunol. 1993 Nov 15;151(10):5338-47
references.pmid: 8228229
references.citation: Cloning Stem Cells. 2007 Fall;9(3):432-49
references.pmid: 17594198
references.citation: Stem Cells. 2008 Jan;26(1):89-98
references.pmid: 17962705
references.citation: Reprod Biomed Online. 2004 Dec;9(6):623-9
references.pmid: 15670408
references.citation: Nature. 1991 Nov 21;354(6350):235-8
references.pmid: 1720508
references.citation: Mol Hum Reprod. 1998 Oct;4(10):966-71
references.pmid: 9809678
references.citation: Immunol Rev. 2005 Oct;207:145-57
references.pmid: 16181333