Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.

CAS  PubMed  Google Scholar 

Yamanaka S. Pluripotent stem cell-based cell therapy–promise and challenges. Cell Stem Cell. 2020;27:523–31.

CAS  PubMed  Google Scholar 

Blau HM, Daley GQ. Stem cells in the treatment of disease. New Engl J Med. 2019;380:1748–60.

CAS  PubMed  Google Scholar 

Alvarez-Dominguez JR, Melton DA. Cell maturation: hallmarks, triggers, and manipulation. Cell. 2022;185:235–49.

CAS  PubMed  Google Scholar 

Marino J, Paster J, Benichou G. Allorecognition by T lymphocytes and allograft rejection. Front Immunol. 2016;7:582.

PubMed  PubMed Central  Google Scholar 

Dausset J. Iso-leuco-anticorps. Acta Haematol-basel. 1958;20:156–66.

CAS  Google Scholar 

Thorsby E. A short history of HLA. Tissue Antigens. 2009;74:101–16.

CAS  PubMed  Google Scholar 

Parham P. Molecular definition of the transplantation antigens. Febs J. 2018;285:2728–45.

CAS  PubMed  Google Scholar 

Doherty PC, Zinkernagel RM. A biological role for the major histocompatibility antigens. Lancet. 1975;305:1406–9.

Google Scholar 

Li F, Atz ME, Reed EF. Human leukocyte antigen antibodies in chronic transplant vasculopathy–mechanisms and pathways. Curr Opin Immunol. 2009;21:557–62.

CAS  PubMed  PubMed Central  Google Scholar 

Badin RA, Bugi A, Williams S, Vadori M, Michael M, Jan C, et al. MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates. Nat Commun. 2019;10:4357.

Google Scholar 

Griffioen M, van Bergen CAM, Falkenburg JHF. Autosomal minor histocompatibility antigens: how genetic variants create diversity in immune targets. Front Immunol. 2016;7:100.

PubMed  PubMed Central  Google Scholar 

Oostvogels R, Lokhorst HM, Mutis T. Minor histocompatibility Ags: identification strategies, clinical results and translational perspectives. Bone Marrow Transpl. 2016;51:163–71.

CAS  Google Scholar 

Summers C, Sheth VS, Bleakley M. Minor histocompatibility antigen-specific T cells. Front Pediatr. 2020;8:284.

PubMed  PubMed Central  Google Scholar 

Zhao T, Zhang Z-N, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature. 2011;474:212–5.

CAS  PubMed  Google Scholar 

Lang F, Schrörs B, Löwer M, Türeci Ö, Sahin U. Identification of neoantigens for individualized therapeutic cancer vaccines. Nat Rev Drug Discov. 2022;21:261–82.

CAS  PubMed  PubMed Central  Google Scholar 

Deuse T, Hu X, Agbor-Enoh S, Koch M, Spitzer MH, Gravina A, et al. De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans. Nat Biotechnol. 2019;37:1137–44.

CAS  PubMed  Google Scholar 

Drukker M, Katz G, Urbach A, Schuldiner M, Markel G, Itskovitz-Eldor J, et al. Characterization of the expression of MHC proteins in human embryonic stem cells. Proc Natl Acad Sci. 2002;99:9864–9.

CAS  PubMed  PubMed Central  Google Scholar 

Drukker M, Benvenisty N. The immunogenicity of human embryonic stem-derived cells. Trends Biotechnol. 2004;22:136–41.

CAS  PubMed  Google Scholar 

de Almeida PE, Ransohoff JD, Nahid A, Wu JC. Immunogenicity of pluripotent stem cells and their derivatives. Circ Res. 2013;112:549–61.

PubMed  PubMed Central  Google Scholar 

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-rNA–guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337:816–21.

CAS  PubMed  PubMed Central  Google Scholar 

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas Systems. Science. 2013;339:819–23.

CAS  PubMed  PubMed Central  Google Scholar 

Doudna JA. The promise and challenge of therapeutic genome editing. Nature. 2020;578:229–36.

CAS  PubMed  PubMed Central  Google Scholar 

Anzalone AV, Koblan LW, Liu DR. Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat Biotechnol. 2020;38:824–44.

CAS  PubMed  Google Scholar 

Cresswell P, Bangia N, Dick T, Diedrich G. The nature of the MHC class I peptide loading complex. Immunol Rev. 1999;172:21–8.

CAS  PubMed  Google Scholar 

Ploegh HL, Orr HT, Strominger JL. Major histocompatibility antigens: the human (HLA-A,-B,-C) and murine (H-2K, H-2D) class I molecules. Cell. 1981;24:287–99.

CAS  PubMed  Google Scholar 

Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, et al. Combined genetic inactivation of β2-microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell. 2011;20:728–40.

CAS  PubMed  PubMed Central  Google Scholar 

Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24:679–90.

CAS  PubMed  PubMed Central  Google Scholar 

Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane J-P, et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat Commun. 2017;8:1136.

PubMed  PubMed Central  Google Scholar 

Riolobos L, Hirata RK, Turtle CJ, Wang P-RR, Gornalusse GG, Zavajlevski M, et al. HLA engineering of human pluripotent stem cells. Mol Ther. 2013;21:1232–41.

CAS  PubMed  PubMed Central  Google Scholar 

• Gornalusse GG, Hirata RK, Funk SE, Riolobos L, Lopes VS, Manske G, et al. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat Biotechnol. 2017;35:765–72. This study shows that single-chain HLAB2M fusion constructs protect HLA-deficient hPSC from NK cell attack.

CAS  PubMed  PubMed Central  Google Scholar 

Lu P, Chen J, He L, Ren J, Chen H, Rao L, et al. Generating hypoimmunogenic human embryonic stem cells by the disruption of beta 2-microglobulin. Stem Cell Rev Rep. 2013;9:806–13.

CAS  PubMed  Google Scholar 

Feng Q, Shabrani N, Thon JN, Huo H, Thiel A, Machlus KR, et al. Scalable generation of universal platelets from human induced pluripotent stem cells. Stem Cell Rep. 2014;3:817–31.

CAS  Google Scholar 

Mandal PK, Ferreira LM, Collins R, Meissner TB, Boutwell CL, Friesen M, et al. Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9. Cell Stem Cell. 2014;15:643–52.

CAS  PubMed  PubMed Central  Google Scholar 

Mattapally S, Pawlik KM, Fast VG, Zumaquero E, Lund FE, Randall TD, et al. Human leukocyte antigen class I and II knockout human induced pluripotent stem cell-derived cells: universal donor for cell therapy. J Am Heart Assoc. 2018;7:e010239.

CAS  PubMed  PubMed Central  Google Scholar 

•• Deuse T, Hu X, Gravina A, Wang D, Tediashvili G, De C, et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol. 2019;37:252–8. This study argues that high-level CD47 can protect HLA-deficient cells from NK cell-mediated lysis.

CAS  PubMed  PubMed Central  Google Scholar 

Merola J, Reschke M, Pierce RW, Qin L, Spindler S, Baltazar T, et al. Progenitor-derived human endothelial cells evade alloimmunity by CRISPR/Cas9-mediated complete ablation of MHC expression. JCI Insight. 2019;4:e129739.

PubMed Central  Google Scholar 

•• Han X, Wang M, Duan S, Franco PJ, Kenty JH, Hedrick P, et al. Generation of hypoimmunogenic human pluripotent stem cells. Proc Nat Acad Sci. 2019;116:10441–6. This study combines multiplexing to specifically ablate the expression of the polymorphic HLA class Ia genes with safe harbor locus insertion of the innate immune regulators PD-L1, HLA-G, and CD47.

Li Y-R, Zhou Y, Kim YJ, Zhu Y, Ma F, Yu J, et al. Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy. Cell Rep Med. 2021;2:100449.

CAS  PubMed  PubMed Central  Google Scholar 

• Wang B, Iriguchi S, Waseda M, Ueda N, Ueda T, Xu H, et al. Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells. Nat Biomed Eng. 2021;5:429–40. This study demonstrates that cytotoxic CD8+ T cells can be differentiated from immune-edited iPSC.

•• Gerace D, Zhou Q, Kenty JH-R, Sintov E, Boulanger KR, Wang X, et al. Secreted cytokines provide local immune tolerance for human stem cell-derived islets. BioRxiv; 2022. https://doi.org/10.1101/2022.05.09.487072. This study suggests that expression of immunosuppressive cytokines in combination with a version of IL-2 that preferentially favors the outgrowth of regulatory T cells (Treg) protects hPSC from immune rejection even in the presence of an intact HLA barrier.

Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9:503–10.

CAS  PubMed  Google Scholar 

Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L. Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol. 2012;12:239–52.

CAS  PubMed  PubMed Central  Google Scholar 

Liao N-S, Bix M, Zijlstra M, Jaenisch R, Raulet D. MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. Science. 1991;253:199–202.

CAS  PubMed  Google Scholar 

Bix M, Liao N-S, Zijlstra M, Loring J, Jaenisch R, Raulet D. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature. 1991;349:329–31.

CAS  PubMed  Google Scholar 

Zhao L, Teklemariam T, Hantash BM. Heterelogous expression of mutated HLA-G decreases immunogenicity of human embryonic stem cells and their epidermal derivatives. Stem Cell Res. 2014;13:342–54.

CAS