Generating hESCs with reduced immunogenicity by disrupting TAP1 or TAPBP

Biosci Biotechnol Biochem. 2016 Aug;80(8):1484-91. doi: 10.1080/09168451.2016.1165601. Epub 2016 Apr 12.

Abstract

Human embryonic stem cells (hESCs) are thought to be a promising resource for cell therapy, while it has to face the major problem of graft immunological rejection. Major histocompatibility complex (MHC) class I expressed on the cell surface is the major cause of graft rejection. Transporter associated with antigen presentation 1 (TAP1) and TAP-associated glycoprotein (TAPBP) play important roles in regulating MHC class I expression. In this study, we generated TAP1- and TAPBP-deficient hESC lines, respectively, using transcription activator-like effector nucleases technique. These cells showed deficient expression of MHC class I on the cell surface and reduced immunogenicity compared with wild types, but maintained normal pluripotency, karyotypes, and differentiation ability. Thus, our findings are instrumental in developing a universal cell resource with both pluripotency and hypo-immunogenicity for transplantation therapy in the future.

Keywords: TAP-associated glycoprotein (TAPBP); immune rejection; major histocompatibility complex (MHC) class I; transcription activator-like effector nucleases (TALEN); transporter associated with antigen presentation 1 (TAP1).

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2 / deficiency
  • ATP Binding Cassette Transporter, Subfamily B, Member 2 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 2 / immunology*
  • Animals
  • Base Sequence
  • Gene Expression
  • Genetic Engineering
  • Graft Survival
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Human Embryonic Stem Cells / cytology
  • Human Embryonic Stem Cells / immunology*
  • Humans
  • Injections, Intramuscular
  • Membrane Transport Proteins / deficiency
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / immunology
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / immunology*
  • Stem Cell Transplantation*
  • Transplantation, Heterologous

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • Histocompatibility Antigens Class I
  • Membrane Transport Proteins
  • TAP1 protein, human
  • tapasin