Characterization of the Expression of MHC Proteins in Human Embryonic Stem Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 Jul 13

PMID 12114532

Citations 208

Authors

Micha Drukker

Gil Katz

Achia Urbach

Maya Schuldiner

Gal Markel

Joseph Itskovitz-Eldor

Benjamin Reubinoff

Ofer Mandelboim

Nissim Benvenisty

Affiliations

Soon will be listed here.

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-gamma but not with IFN-alpha or -beta. 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.

Citing Articles

Immune Evasion in Stem Cell-Based Diabetes Therapy-Current Strategies and Their Application in Clinical Trials.

Mu-U-Min R, Diane A, Allouch A, Al-Siddiqi H Biomedicines. 2025; 13(2).

PMID: 40002796 PMC: 11853723. DOI: 10.3390/biomedicines13020383.

Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression.

Adcox H, Hunt J, Allen P, Siff T, Rodino K, Ottens A Nat Commun. 2024; 15(1):8069.

PMID: 39277599 PMC: 11401901. DOI: 10.1038/s41467-024-52119-6.

Low Immunogenicity of Keratinocytes Derived from Human Embryonic Stem Cells.

Shen J, Zeng X, Lv H, Jin Y, Liu Y, Lian W Cells. 2024; 13(17.

PMID: 39273019 PMC: 11393835. DOI: 10.3390/cells13171447.

Development of a baculoviral CRISPR/Cas9 vector system for beta-2-microglobulin knockout in human pluripotent stem cells.

Xiang Z, Ye Q, Zhao Z, Wang N, Li J, Zou M Mol Genet Genomics. 2024; 299(1):74.

PMID: 39085666 DOI: 10.1007/s00438-024-02167-w.

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review.

Sheikhlary S, Lopez D, Moghimi S, Sun B Biomolecules. 2024; 14(4).

PMID: 38672519 PMC: 11048403. DOI: 10.3390/biom14040503.

References

Barnstable C, Bodmer W, Brown G, Galfre G, Milstein C, Williams A . Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978; 14(1):9-20. DOI: 10.1016/0092-8674(78)90296-9. View

Cibelli J, Lanza R, West M, Ezzell C . The first human cloned embryo. Sci Am. 2002; 286(1):44-51. DOI: 10.1038/scientificamerican0102-44. View

Stam N, Spits H, Ploegh H . Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol. 1986; 137(7):2299-306. View

Shimizu Y, Geraghty D, Koller B, Orr H, Demars R . Transfer and expression of three cloned human non-HLA-A,B,C class I major histocompatibility complex genes in mutant lymphoblastoid cells. Proc Natl Acad Sci U S A. 1988; 85(1):227-31. PMC: 279517. DOI: 10.1073/pnas.85.1.227. View

Desoye G, Dohr G, Motter W, Winter R, Urdl W, Pusch H . Lack of HLA class I and class II antigens on human preimplantation embryos. J Immunol. 1988; 140(12):4157-9. View

Beddington R, Robertson E . An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development. 1989; 105(4):733-7. DOI: 10.1242/dev.105.4.733. View

Kovats S, Main E, Librach C, Stubblebine M, Fisher S, Demars R . A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990; 248(4952):220-3. DOI: 10.1126/science.2326636. View

Ljunggren H, Karre K . In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today. 1990; 11(7):237-44. DOI: 10.1016/0167-5699(90)90097-s. View

Bailey K, Drago J, Bartlett P . Neuronal progenitors identified by their inability to express class I histocompatibility antigens in response to interferon-gamma. J Neurosci Res. 1994; 39(2):166-77. DOI: 10.1002/jnr.490390207. View

10.

Jurisicova A, Casper R, Maclusky N, Mills G, Librach C . HLA-G expression during preimplantation human embryo development. Proc Natl Acad Sci U S A. 1996; 93(1):161-5. PMC: 40198. DOI: 10.1073/pnas.93.1.161. View

11.

Mandelboim O, Reyburn H, Vales-Gomez M, Pazmany L, Colonna M, Borsellino G . Protection from lysis by natural killer cells of group 1 and 2 specificity is mediated by residue 80 in human histocompatibility leukocyte antigen C alleles and also occurs with empty major histocompatibility complex molecules. J Exp Med. 1996; 184(3):913-22. PMC: 2192787. DOI: 10.1084/jem.184.3.913. View

12.

Rouas-Freiss N, Goncalves R, Menier C, Dausset J, Carosella E . Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci U S A. 1997; 94(21):11520-5. PMC: 23525. DOI: 10.1073/pnas.94.21.11520. View

13.

Lee N, Goodlett D, Ishitani A, Marquardt H, Geraghty D . HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences. J Immunol. 1998; 160(10):4951-60. View

14.

Pessino A, Sivori S, Bottino C, Malaspina A, Morelli L, Moretta L . Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity. J Exp Med. 1998; 188(5):953-60. PMC: 3207313. DOI: 10.1084/jem.188.5.953. View

15.

Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V . Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391):1145-7. DOI: 10.1126/science.282.5391.1145. View

16.

Cantoni C, Bottino C, Vitale M, Pessino A, Augugliaro R, Malaspina A . NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily. J Exp Med. 1999; 189(5):787-96. PMC: 2192947. DOI: 10.1084/jem.189.5.787. View

17.

Mandelboim O, Malik P, Davis D, Jo C, Boyson J, Strominger J . Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity. Proc Natl Acad Sci U S A. 1999; 96(10):5640-4. PMC: 21913. DOI: 10.1073/pnas.96.10.5640. View

18.

Pende D, Parolini S, Pessino A, Sivori S, Augugliaro R, Morelli L . Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J Exp Med. 1999; 190(10):1505-16. PMC: 2195691. DOI: 10.1084/jem.190.10.1505. View

19.

Reubinoff B, Pera M, Fong C, Trounson A, Bongso A . Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol. 2000; 18(4):399-404. DOI: 10.1038/74447. View

20.

Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M . Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med. 2000; 6(2):88-95. PMC: 1949933. View