PMID- 28504668
OWN - NLM
STAT- MEDLINE
DCOM- 20170821
LR  - 20220321
IS  - 1546-1696 (Electronic)
IS  - 1087-0156 (Print)
IS  - 1087-0156 (Linking)
VI  - 35
IP  - 8
DP  - 2017 Aug
TI  - HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by 
      NK cells.
PG  - 765-772
LID - 10.1038/nbt.3860 [doi]
AB  - Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the 
      rejection of pluripotent stem cell (PSC)-derived products in allogeneic 
      recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface 
      expression of all class I molecules, but leaves the cells vulnerable to lysis by 
      natural killer (NK) cells. Here we show that this 'missing-self' response can be 
      prevented by forced expression of minimally polymorphic HLA-E molecules. We use 
      adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the 
      B2M locus in human PSCs in a manner that confers inducible, regulated, surface 
      expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M 
      and a peptide antigen), without surface expression of HLA-A, B or C. These 
      HLA-engineered PSCs and their differentiated derivatives are not recognized as 
      allogeneic by CD8(+) T cells, do not bind anti-HLA antibodies and are resistant 
      to NK-mediated lysis. Our approach provides a potential source of universal donor 
      cells for applications where the differentiated derivatives lack HLA class II 
      expression.
FAU - Gornalusse, German G
AU  - Gornalusse GG
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
FAU - Hirata, Roli K
AU  - Hirata RK
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
FAU - Funk, Sarah E
AU  - Funk SE
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
FAU - Riolobos, Laura
AU  - Riolobos L
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
FAU - Lopes, Vanda S
AU  - Lopes VS
AD  - Center for Stem Cell Biology and Engineering, Department of Molecular, Cellular, 
      and Developmental Biology, University of California, Santa Barbara, USA.
FAU - Manske, Gabriel
AU  - Manske G
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
FAU - Prunkard, Donna
AU  - Prunkard D
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
FAU - Colunga, Aric G
AU  - Colunga AG
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
FAU - Hanafi, Laila-Aicha
AU  - Hanafi LA
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, USA.
FAU - Clegg, Dennis O
AU  - Clegg DO
AD  - Center for Stem Cell Biology and Engineering, Department of Molecular, Cellular, 
      and Developmental Biology, University of California, Santa Barbara, USA.
FAU - Turtle, Cameron
AU  - Turtle C
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, USA.
FAU - Russell, David W
AU  - Russell DW
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
AD  - Department of Biochemistry, University of Washington, Seattle, Washington, USA.
LA  - eng
GR  - R01 DK055759/DK/NIDDK NIH HHS/United States
GR  - R01 HL130770/HL/NHLBI NIH HHS/United States
GR  - T32 HL007093/HL/NHLBI NIH HHS/United States
GR  - U54 DK106829/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20170515
PL  - United States
TA  - Nat Biotechnol
JT  - Nature biotechnology
JID - 9604648
RN  - 0 (HLA Antigens)
SB  - IM
CIN - Nat Biotechnol. 2017 Aug 8;35(8):722-723. PMID: 28787417
MH  - Animals
MH  - Female
MH  - Graft Rejection/immunology
MH  - HLA Antigens/chemistry/genetics/*immunology
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Mice
MH  - Pluripotent Stem Cells/chemistry/cytology/*immunology
MH  - Transplants/chemistry/cytology/*immunology
PMC - PMC5548598
MID - NIHMS863048
EDAT- 2017/05/16 06:00
MHDA- 2017/08/22 06:00
PMCR- 2017/11/15
CRDT- 2017/05/16 06:00
PHST- 2016/05/09 00:00 [received]
PHST- 2017/03/24 00:00 [accepted]
PHST- 2017/05/16 06:00 [pubmed]
PHST- 2017/08/22 06:00 [medline]
PHST- 2017/05/16 06:00 [entrez]
PHST- 2017/11/15 00:00 [pmc-release]
AID - nbt.3860 [pii]
AID - 10.1038/nbt.3860 [doi]
PST - ppublish
SO  - Nat Biotechnol. 2017 Aug;35(8):765-772. doi: 10.1038/nbt.3860. Epub 2017 May 15.