Neuronal MHC-I display in T-cell mediated neurodegeneration
Molecular Neurodegeneration volume 8, Article number: P38 (2013)
Parkinson’s disease (PD) and other disorders feature the degeneration of ventral midbrain (VM) catecholamine neurons. Recent data suggest that neuroinflammatory mechanisms contribute to a cascade of events leading to chronic neuronal degeneration.
In primary murine neuronal cultures, substantia nigra (SN) and locus coeruleus (LC) neurons are induced to express the major histocompatibility class I complex (MHC-I) by the proinflammatory cytokine, γ-interferon, L-DOPA, or conditioned medium from microglia exposed to α-synuclein or NM. SN DA neurons, moreover, process the foreign protein ovalbumin to an antigenic peptide that is presented by their MHC-I and triggers their specific destruction by CD8+ killer T-cells. In human postmortem samples, we find by immunolabel, mRNA profiling, and proteomic analysis that neuromelanin (NM)-containing catecholamine SN and LC neurons in adult human control and PD brains express MHC-I, often in proximity to CD8+ T-cells. These data reveal a novel inflammatory T-cell mediated neurodegenerative processes that could underlie neuronal death.
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Cebrián, C., Zucca, F., Zecca, L. et al. Neuronal MHC-I display in T-cell mediated neurodegeneration. Mol Neurodegeneration 8 (Suppl 1), P38 (2013). https://doi.org/10.1186/1750-1326-8-S1-P38