Expression of MHC class I proteins and their antigen processing chaperones in mouse embryonic stem cells from fertilized and parthenogenetic embryos

摘要

Embryonic stem (ES) cells are pluripotent cells with the potential to differentiate into cells or tissues that may be used for transplantation therapy. Parthenogenetic ES cells have been recently derived from both mouse and human oocytes and hold promise as a cell source which is histocompatible to the oocyte donor. Due to the importance of major histocompatibility complex (MHC) antigens in mediating tissue rejection or acceptance, we examined levels of mRNA and protein expression of MHC class I proteins, as well as several MHC class I antigen processing and presentation chaperones, in mouse embryonic stem cells derived from both fertilized (fES) and parthenogenetic (pES) embryos. We found that H-2K, Qa-2, TAP1, TAP2 and tapasin mRNAs were all expressed at low levels in undifferentiated and differentiating ES cells, and were significantly upregulated in response to interferon-γ (IFN-γ) treatment following 14 days of differentiation. Likewise, expression of H-2K^b and H-2K^k proteins were upregulated to detectable levels by IFN-γ after 14 days of differentiation, but Qa-2 protein expression remained low or absent. We also found that MHC class I, TAP1, TAP2, and tapasin mRNAs were all expressed at very low levels in ES cells compared to T cells, suggesting transcriptional regulation of these genes in ES cells. Calnexin, a chaperone molecule involved in other pathways than MHC expression, had mRNA levels that were similar in ES cells and T cells, and was not upregulated by IFN-γ in ES cells. Overall, embryonic stem cells derived from fertilized embryos and parthenogenetic embryos displayed remarkably similar patterns of gene expression at the mRNA and protein levels. The similarity between the fES and pES cell lines in regard to expression of MHC class I and antigen processing machinery provides evidence for the potential usefulness of parthenogenetic ES cells in transplantation therapy.