MHC class I manipulation on cell surfaces by gene transfer of anti-MHC class I intrabodies--a tool for decreased immunogenicity of allogeneic tissue and cell transplants.
Intrabodies (IB) are suitable tools to down-regulate the expression of cell surface molecules in general. In this work, the appearance of major histocompatibility (MHC) class I molecules on the cell surface could be prevented by the expression of intracellularly localized anti-MHC class I antibodies. The expression of MHC antigens presenting intracellularly synthetised peptides on the cell surface is the predominant reason for immunologic detection and rejection of allogeneic cell and tissue transplants. Allogeneic keratinocyte sheets might be a suitable tool for skin grafting. Within this study primary rat keratinocytes have been transfected with anti-MHC I-IB. Strong IB-expressing cells showed a MHC I "knockout" phenotype. The cells did not exhibit any significant alterations compared to non-transfected cells: the cell growth and the expression of other surface molecules were unaltered. Merely an enhanced intracellular accumulation of MHC I molecules could be detected. Notably, IB-expressing keratinocytes displayed a reduced susceptibility to allogeneic cytotoxic T cells in vitro compared to unmodified cells with a normal level of MHC I surface expression. These MHC I-deficient keratinocytes might be utilized in tissue-engineered allogeneic non-immunogeneic skin transplants. The principle of MHC class I manipulation in general can be used for other allogeneic cell and tissue-engineered transplants as well.
Busch
Annette
A
Department of Medical Immunology, Medical School (Charité), Humboldt University Berlin, Schumannstrasse 20/21, D-10098 Berlin, Germany.
Marasco
Wayne A
WA
Doebis
Cornelia
C
Volk
Hans-Dieter
HD
Seifert
Martina
M
D000818:Animals; D000906:Antibodies / Q000235:genetics* / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D005805:Genes, MHC Class I; D006801:Humans; D015603:Keratinocytes / Q000276:immunology; D051381:Rats; D014184:Transplantation, Homologous / Q000276:immunology*
D000906:Antibodies; D000954:Antigens, Surface