Characterization of the expression of MHC proteins in human embryonic stem cells

Micha Drukker, Gil Katz, Achia Urbach, Maya Schuldiner, Gal Markel, Joseph Itskovitz-Eldor, Benjamin Reubinoff, Ofer Mandelboim, Nissim Benvenisty

Research output: Contribution to journalArticlepeer-review

Abstract

Human embryonic stem (ES) cells are pluripotent cells that may be used in transplantation medicine. These cells can be induced to differentiate into cells from the three embryonic germ layers both in vivo and in vitro. To determine whether human ES cells might be rejected after transplantation, we examined cell surface expression of the MHC proteins in these cells. Our results show very low expression levels of MHC class I (MHC-I) proteins on the surface of human ES cells that moderately increase on in vitro or in vivo differentiation. A dramatic induction of MHC-I proteins was observed when the cells were treated with IFN-γ but not with IFN-α or-β. However, all three IFNs induced expression of MHC-I proteins in differentiated human ES cells. MHC-II proteins and HLA-G were not expressed on the surface of undifferentiated or differentiated cells. Ligands for natural killer cell receptors were either absent or expressed in very low levels in human ES cells and in their differentiated derivatives. In accordance, natural killer cytotoxic assays demonstrated only limited lysis of both undifferentiated and differentiated cells. To initiate a histocompatibility databank of human ES cells, we have isotyped several of the published ES cell lines for their human leukocyte antigens. In conclusion, our results demonstrate that human ES cells can express high levels of MHC-I proteins and thus may be rejected on transplantation.

Original languageEnglish
Pages (from-to)9864-9869
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number15
DOIs
StatePublished - 23 Jul 2002
Externally publishedYes

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