Developmental expression and localization of MHC class I molecules in the human central nervous system

Abstract

Recent animal studies have found neuronal expression of major histocompatibility complex (MHC) class I in the central nervous system (CNS). However, the developmental expression profiles of MHC class I in human CNS remain unclear. Here, we systemically evaluate the expression and subcellular localization of MHC class I molecules during human CNS development using immunohistochemistry and immunofluorescence. Between the age of 20-33 gestational weeks (GW), MHC class I expression was relatively absent in the cerebral cortex with the exception of a few neurons; however, expression increased rapidly in the cochlear nuclei and in the cerebellar cortical Purkinje cells while increasing slowly in the substantia nigra. Expression was also detected in some nuclei and nerve fibers of the brain stem including the ambiguus nucleus, the locus coeruleus and the solitary tract as early as 20 GW and persisted through 33 GW. These early-stage neural cells with MHC class I protein expression later developed neuronal morphology. 30-33 GW is an important period of MHC class I expression in neurons, and during this period, MHC class I molecules were found to be enriched not only in neuronal cell bodies and neurites but also in nerve fibers and in the surrounding stroma. No expression was detected in the adult brain with exception of the cerebrovascular endothelium. MHC class I molecules displayed greater postsynaptic colocalization in cerebellar Purkinje cells, in the lateral geniculate nucleus and in the cochlear nuclei. These results demonstrate diverse spatiotemporal expression patterns for MHC class I molecules in the prenatal human CNS and strongly support the notion that MHC class I molecules play important roles in both CNS development and plasticity.

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

“…We have proposed that this mechanism underlies the injury of demyelinated axons in multiple sclerosis (MS) 1, 2, 4, 10. Evidence also suggests that MHC I is involved with synaptic pruning during cortical development12, 13, 14, 16, 17, 18, 19, 20, 21 and following injury22, 23, 24, 25 and contributes to neuronal plasticity 16, 17, 26, 27. These findings also suggest that retrogradely induced MHC class I may contribute to the diffuse synaptopathy observed in MS and other neurodegenerative diseases 28, 29, 30, 31, 32, 33, 34, 35.…”

“…[1][2][3][4] Likewise, anterograde and retrograde signaling events propagating in stressed, damaged, or dysfunctional axons are thought to contribute separately to processes involved in both injury and repair in the central nervous system (CNS) [5][6][7][8][9][10] (reviewed in 11). While the expression and function of MHC class I on adult human neurons remains disputed, [12][13][14][15] we previously demonstrated that retrograde interferon gamma (IFNc) signaling induced the expression of major histocompatibility class I (MHC I) molecules in murine axons. 10 Moreover, we found that increased surface expression of peptide-loaded MHC I rendered axons more susceptible to attack by antigen-specific CD8 + T cells.…”

Effect of Sodium Valproate on Cognitive Function and Hippocampus of Rats After Convulsive Status Epilepticus

“…These patterns of synaptic activity produce a long-lasting increase in signal transmission between two neurons [7]. Previous studies found that the hippocampus is part of the limbic system and plays an important role in the consolidation of information from short-term memory to long-term memory, and also affects spatial navigation.…”

Immunobiological properties of neurogenic cells of the fetal brain. І. Expression of molecules with immune properties

“…За допомогою імуногістохімічних та імунофлуоресцентних методів дослідження експресії антигенів МНС протягом розвитку ЦНС людини встановлено, що впродовж 20-33 тиж гестації експресія MHC I класу у корі головного мозку в основному була відсутня, за винятком декількох нейронів; натомість у цей проміжок вона швидко зростала у кохлеарних ядрах та клітинах Пуркіньє кори мозочка та повільно зростала у чорній субстанції [54,55]. Також експресія MHC I візуалізувалась у деяких ядрах і нервових волокнах стовбура мозку.…”

“…Крім того, експресія МНС І регулюється нейрональною активністю і залучається в гомеостатичну регуляцію функції та морфологічної структури синапсів протягом індивідуального розвитку і у відповідь на блокаду нейрональної активності [68]. Нещодавні дослідження підтвердили роль МНС І у розвитку ЦНС, регуляції росту нейритів і синаптичної пластичності преі постнатального мозку, що розвивається [35,54,55,[69][70][71].…”