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The MHC class Ⅰ molecules are considered to be important in the immune system for a long time.However, recently it was reported that they played important roles in brain development and synaptic plasticity.In this study, the expression ofMHC Ⅰ (H-2Kb and H-2Db) mRNAs were investigated in C57BL/6 mice by in situ hybridization and the expression of H-2K/D proteins were analyzed by flow cytometry.We also examined the expression of MHC Ⅰ and β2-microglobulin (β2m) genes in human cerebellar cortex by immunostaining.In the developing cerebellum, hybridization signals of H2-Db were detected from P0 to adult, reaching a peak value at P1 5.The signals were mainly located at the purkinje cells (PCs) layer.The expression patterns of H2-Kb mRNA were the same as H2-Db.Consistent with this, the expression of H-2K/D proteins in PCs increased from P0 to P 15.From then on, it went through a gradually decrease to the level of adult mice.MHC Ⅰ and β2m proteins were both expressed in the early developmental stages of human cerebellar cortex.The expression of MHC Ⅰ genes was enhanced with the development of human cerebellar cortex, but decreased after birth until vanish.The spatial and temporal expression of β2m overlapped mostly with that of MHC Ⅰ molecules, with its expression peak at 29 weeks PMA (postmenstrual age).In mouse cerebellar cortex, the regression from multiple to single climbing fiber innervation of the PCs occurs during development between postnatal days P5 and 15.On the other hand, it has been shown that 28 to 30 weeks PMA are the critical period for the development of synaptic plasticity in human cerebellum.Since MHC Ⅰ expression is particularly high in regions and at times undergoing activity dependent plasticity in cerebellum, we speculate that the expression of classical MHC Ⅰ molecules may regulate the degree of synaptic plasticity in mammalian brain.Moreover, MHC class Ⅰ complex might be required for displaying its function and the MHC Ⅰ acts downstream of synaptic activity could be regulated at the transcriptional level.