Prevention of xenograft rejection by masking donor HLA class I antigens.
Destruction of target cells by cytotoxic T lymphocytes requires the presence of HLA (human lymphocyte antigen) class I antigens on the target cells for adhesion as well as for triggering of the antigen-specific T cell receptor. Rejection of xenogeneic human pancreatic islets and liver was circumvented by masking, before transplantation, donor antigens with F(ab')2 antibody fragments to HLA class I or tissue-specific epitopes. This strategy eliminated the need for recipient immunosuppression and allowed islet xenograft survival beyond 200 days, as demonstrated functionally by C peptide secretion as well as by histology. These in vivo observations are consistent with the importance of donor HLA class I in eliciting graft rejection and have potential applicability to the successful transplantation of other HLA class I-bearing donor tissues.
Faustman
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Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02129.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex; D015703:Antigens, CD / Q000276:immunology; D002096:C-Peptide / Q000097:blood; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D019012:Integrin beta1; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D002096:C-Peptide; D015395:Histocompatibility Antigens Class I; D007140:Immunoglobulin Fab Fragments; D019012:Integrin beta1