MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration
Carolina Cebrián, Fabio A Zucca, Pierluigi Mauri, Julius A Steinbeck, Lorenz Studer, Clemens R Scherzer, Ellen Kanter, Sadna Budhu, Jonathan Mandelbaum, Jean P Vonsattel, Luigi Zecca, John D Loike, David Sulzer, Carolina Cebrián, Fabio A Zucca, Pierluigi Mauri, Julius A Steinbeck, Lorenz Studer, Clemens R Scherzer, Ellen Kanter, Sadna Budhu, Jonathan Mandelbaum, Jean P Vonsattel, Luigi Zecca, John D Loike, David Sulzer
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.
Conflict of interest statement
Competing financial interests
The authors declare no competing financial interests.
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References
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