Inhibition of swine leukocyte antigen-I presentation in transgenic mini-pig cell lines by expressing human cytomegalovirus US6.
Transplant Proc
; 42(10): 4648-50, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-21168753
ABSTRACT
Xenotransplantation using porcine organs may resolve the chronic shortage of donor organs for clinical transplantation if significant immunologic barriers can be overcome. A xenograft can be rejected by T cells, especially CD8(+) cytotoxic T lymphocytes (CTL)-mediated responses, as these cells show cytotoxicity against xenografts by recognition of swine leukocyte antigen (SLA)-I. Peptide translocation is inhibited by the endoplasmic reticulum-resident human cytomegalovirus (HCMV) glycoprotein unique short (US) 6, due to alterations of the transporter associated with antigen processing loading onto MHC class I for antigen presentation to CD8(+) CTL. In this study we transfected the US6 gene into minipig fetal fibroblasts establishing three US6 clonal cell lines. Flow cytometry analysis of US6 clonal cell lines demonstrated a substantial reduction in SLA-I expression. The level of SLA-I expression in US6 clones was decreased to 56.3% compared with the control 42.7%. In CTL assays, the rate of CD8(+) CTL-mediated cytotoxicity was significantly reduced to 35.2% ± 11.7% compared with the control, 79.9% ± 6.5%, (P < .01). These results suggested that HCMV viral protein US6 suppresses the presentation of SLA-I on pig fetal fibroblast cells. This strategy might be used in transgenic pig production to protect porcine organs from CTL-mediated immune rejection.
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Proteínas Virais
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Antígenos de Histocompatibilidade Classe II
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Proteínas de Ligação a RNA
Limite:
Animals
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Humans
Idioma:
En
Revista:
Transplant Proc
Ano de publicação:
2010
Tipo de documento:
Article