It has been considered that the healthy neurons in central nervous system (CNS) do not express major histocompatibility complex (MHC) class Ⅰ molecules.However, recent studies clearly demonstrated the expression of functional MHC class Ⅰ in the mammalian embryonic, neonatal and adult brain.Until now, it remains unclear whether MHC I molecules is selectively expressed in the developing human brain.Therefore,we collected fourteen human brain tissues from fetuses aged from 21 to 31 gestational weeks (GW), one newborn of postnatal 55 days and three adults.The expression pattern of MHC class Ⅰ molecules in the developing hippocampal formation was detected by immunohistochemistry and immunofluorescence.During the prenatal stages, we found that the expression of MHC class Ⅰ was general lower in hippocampal subfields CA1-4 during 20-26GW and was slightly increased in CA 1-2 at 30-31GW.The expression of MHC class Ⅰ in the dentate gyrus (DG) was gradually increased from 23GW to 31GW.These expression was maintained on CA1-4 and DG in postnatal 55 days.It was intriguing that the cells near the middle-deepest pyramidal layer of the subiculum had an obvious expression of MHC class Ⅰ molecules.The expression level was increased from 23GW to 31GW, reached a high level at 30-31GW and maintained till postnatal 55days.There was almost no MHC class Ⅰ immunoactivity in entorhinal cortex except a few pyramidal cells in layer Ⅲ to Ⅵ.No expression of MHC class Ⅰ was found on all hippocampal formation in adult.The heavy chain and light chain of MHC class Ⅰ was coexpressed in some cells of the developing hippocampal formation at 30-31GW.In order to identify the cell types that express MHC class Ⅰ protein in the hippocampal formation, double-labeling immunofluorescence was performed at 30-31GW.MHC class Ⅰ was mainly expressed in neurons but not in astrocytes and most MHC class Ⅰ-expressing neurons were glutamatergic neurons.In conclusion, there was different expression of MHC class Ⅰ in the subfields of the developing hippocampus.The expression of MHC class Ⅰ protein in subiculum was obvious, which was entirely different from other species.The spatial and temporal expression pattern of MHC class Ⅰ molecules observed in this study was human specific.