title: MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration.
abstract: Subsets of rodent neurons are reported to express major histocompatibility complex class I (MHC-I), but such expression has not been reported in normal adult human neurons. Here we provide evidence from immunolabel, RNA expression and mass spectrometry analysis of postmortem samples that human catecholaminergic substantia nigra and locus coeruleus neurons express MHC-I, and that this molecule is inducible in human stem cell-derived dopamine (DA) neurons. Catecholamine murine cultured neurons are more responsive to induction of MHC-I by gamma-interferon than other neuronal populations. Neuronal MHC-I is also induced by factors released from microglia activated by neuromelanin or alpha-synuclein, or high cytosolic DA and/or oxidative stress. DA neurons internalize foreign ovalbumin and display antigen derived from this protein by MHC-I, which triggers DA neuronal death in the presence of appropriate cytotoxic T cells. Thus, neuronal MHC-I can trigger antigenic response, and catecholamine neurons may be particularly susceptible to T-cell-mediated cytotoxic attack.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Cebrián
authors.affiliation: Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milano 20090, Italy.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Zucca
authors.affiliation: Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milano 20090, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Mauri
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Julius A
authors.initials: JA
authors.lastname: Steinbeck
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Studer
authors.affiliation: The Neurogenomics Laboratory, Harvard Medical School and Brigham and Women's Hospital, Cambridge, Massachusetts 02139, USA.
authors.forename: Clemens R
authors.initials: CR
authors.lastname: Scherzer
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kanter
authors.affiliation: Sloan Kettering Memorial Hospital, New York, New York, USA.
authors.forename: Sadna
authors.initials: S
authors.lastname: Budhu
authors.affiliation: Discovery Oncology Biology, Takeda Pharmaceuticals International Co., 40 Landsdowne Street, Cambridge, MA 021369, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mandelbaum
authors.affiliation: New York Brain Bank, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Jean P
authors.initials: JP
authors.lastname: Vonsattel
authors.affiliation: Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milano 20090, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Zecca
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Loike
authors.affiliation: 1] Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA [2] Department of Psychiatry, Columbia University Medical Center, New York, New York 10032, USA [3] Department of Pharmacology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sulzer
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002470:Cell Survival; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D008543:Melanins; D012333:RNA, Messenger; D051844:alpha-Synuclein; C014121:neuromelanin; D007371:Interferon-gamma; D004298:Dopamine
references.citation: Cell Mol Life Sci. 2011 May;68(9):1533-41
references.pmid: 21390546
references.citation: Science. 2003 Oct 31;302(5646):841
references.pmid: 14593171
references.citation: Behav Brain Res. 2013 Jan 1;236(1):270-282
references.pmid: 22985845
references.citation: Mult Scler. 2006 Oct;12(5):558-64
references.pmid: 17086900
references.citation: Neurology. 1988 Aug;38(8):1285-91
references.pmid: 3399080
references.citation: Cell Immunol. 1993 Sep;150(2):447-52
references.pmid: 8370082
references.citation: J Exp Med. 2010 Jan 18;207(1):223-35
references.pmid: 20065066
references.citation: Science. 1995 Jul 28;269(5223):549-52
references.pmid: 7624779
references.citation: Science. 1997 Jun 27;276(5321):2045-7
references.pmid: 9197268
references.citation: Trends Neurosci. 2009 May;32(5):249-56
references.pmid: 19307031
references.citation: Neurotox Res. 2011 Jan;19(1):63-72
references.pmid: 19957214
references.citation: Ann Neurol. 2002 Mar;51(3):311-8
references.pmid: 11891826
references.citation: Dev Neurobiol. 2008 Jul;68(8):997-1006
references.pmid: 18418877
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17843-8
references.pmid: 15591351
references.citation: Cell. 1994 Jan 14;76(1):17-27
references.pmid: 8287475
references.citation: Nature. 1984 Aug 23-29;310(5979):688-91
references.pmid: 6433204
references.citation: Exp Neurol. 1998 Apr;150(2):282-95
references.pmid: 9527898
references.citation: Sci Transl Med. 2010 Oct 6;2(52):52ra73
references.pmid: 20926834
references.citation: Tissue Antigens. 2005 Apr;65(4):301-69
references.pmid: 15787720
references.citation: Nature. 2012 Jun 28;486(7404):545-8
references.pmid: 22722867
references.citation: Curr Opin Immunol. 2004 Feb;16(1):67-75
references.pmid: 14734112
references.citation: Learn Mem. 2013 Sep 01;20(9):505-17
references.pmid: 23959708
references.citation: Eur J Immunol. 2000 Dec;30(12):3623-33
references.pmid: 11169405
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11869-74
references.pmid: 11050221
references.citation: Arq Neuropsiquiatr. 2009 Sep;67(3A):715-6
references.pmid: 19722060
references.citation: Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S52-4
references.pmid: 22166454
references.citation: Neuron. 1998 Sep;21(3):505-20
references.pmid: 9768838
references.citation: Science. 2000 Dec 15;290(5499):2155-9
references.pmid: 11118151
references.citation: Nat Rev Neurosci. 2007 Jan;8(1):57-69
references.pmid: 17180163
references.citation: PLoS Pathog. 2008 Feb 8;4(2):e28
references.pmid: 18282092
references.citation: J Clin Invest. 2009 Jan;119(1):182-92
references.pmid: 19104149
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6828-33
references.pmid: 17420446
references.citation: Neurotherapeutics. 2010 Oct;7(4):354-65
references.pmid: 20880500
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17567-72
references.pmid: 18988735
references.citation: J Neuroinflammation. 2013 Jan 24;10:12
references.pmid: 23347564
references.citation: Brain. 2009 Jul;132(Pt 7):1795-809
references.pmid: 19052140
references.citation: Traffic. 2001 Feb;2(2):124-37
references.pmid: 11247303
references.citation: J Clin Invest. 2008 Feb;118(2):777-88
references.pmid: 18172548
references.citation: NeuroRx. 2004 Jan;1(1):139-54
references.pmid: 15717014
references.citation: Front Biosci (Elite Ed). 2013 Jan 01;5:1-11
references.pmid: 23276965
references.citation: J Biol Chem. 2005 Jun 3;280(22):21212-9
references.pmid: 15817478
references.citation: Nature. 2011 Nov 06;480(7378):547-51
references.pmid: 22056989
references.citation: Genome Biol. 2004;5(10):R80
references.pmid: 15461798
references.citation: Curr Mol Pharmacol. 2011 Jun 15;:
references.pmid: 21675953
references.citation: Acta Neuropathol. 2000 Oct;100(4):395-402
references.pmid: 10985698
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9843-8
references.pmid: 15210960
references.citation: Science. 2001 Nov 9;294(5545):1346-9
references.pmid: 11701929
references.citation: J Virol. 2010 Jun;84(11):5485-93
references.pmid: 20357096
references.citation: Neurosci Lett. 2007 Feb 27;414(1):94-7
references.pmid: 17196747
references.citation: Glia. 2007 Aug 15;55(11):1178-88
references.pmid: 17600340
references.citation: J Neuroimmune Pharmacol. 2013 Mar;8(1):94-117
references.pmid: 23054368
references.citation: J Immunol. 2013 Mar 15;190(6):2791-806
references.pmid: 23418629
references.citation: J Neurosci. 2009 Dec 9;29(49):15397-409
references.pmid: 20007464
references.citation: PLoS Pathog. 2011 Nov;7(11):e1002393
references.pmid: 22114563
references.citation: Parkinsons Dis. 2012;2012:920953
references.pmid: 22966478
references.citation: Brain Res. 1990 Jul 23;523(2):273-80
references.pmid: 2400911
references.citation: Nat Neurosci. 2011 Apr;14(4):442-51
references.pmid: 21358642
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16999-7004
references.pmid: 20837535
references.citation: Neurobiol Aging. 2012 Jul;33(7):1411-26
references.pmid: 21482445
references.citation: Neurochem Res. 2013 Feb;38(2):273-81
references.pmid: 23124394
references.citation: Acta Neuropathol. 2005 Feb;109(2):141-50
references.pmid: 15619128
references.citation: Brain Res. 2013 Sep 5;1529:26-38
references.pmid: 23838325
references.citation: Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1529-34
references.pmid: 8643666
references.citation: Arch Biochem Biophys. 2004 Mar 1;423(1):88-96
references.pmid: 14871471
references.citation: Nat Neurosci. 2011 Jun;14(6):694-6
references.pmid: 21572432
references.citation: Brain Res. 1995 Jun 5;682(1-2):133-43
references.pmid: 7552304
references.citation: Neurochem Res. 2013 Feb;38(2):290-9
references.pmid: 23161087
references.citation: Neuron. 2009 Apr 30;62(2):218-29
references.pmid: 19409267