Genetically modified HLA class I molecules able to inhibit human NK cells without provoking alloreactive CD8+ CTLs
| Autor: | Gerald L. Waneck, Alexandra F. Sharland, Susan L. Saidman, Aimee E. Cestra, Amy Patel, Josie Han Lee |
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| Rok vydání: | 2002 |
| Předmět: |
Cytotoxicity
Immunologic Immunology Genetic Vectors Dose-Response Relationship Immunologic Down-Regulation Human leukocyte antigen HLA-C Antigens Biology Lymphocyte Activation Transfection Cell Line Immunophenotyping Interleukin 21 Receptors KIR medicine Immunology and Allergy Humans Receptors Immunologic Cell Line Transformed Aspartic Acid Cell Death Effector Lysine Cytotoxicity Tests Immunologic Lymphocyte Subsets Genetically modified organism Clone Cells Killer Cells Natural medicine.anatomical_structure Interleukin 12 Cancer research Mutagenesis Site-Directed Bone marrow CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 168(7) |
| ISSN: | 0022-1767 |
| Popis: | Human NK cells are likely to be important effectors of xenograft rejection. Expression of HLA class I molecules by transfected porcine cells can protect them from human NK cell-mediated lysis; however, this strategy has the potential to augment the anti-graft response by recipient CD8+ T cells recognizing foreign pig peptides presented by HLA. In this study we show that the introduction of a mutation (D227K) in the α3 domain of HLA-Cw3 abrogates its recognition by CD8-dependent T cells but leaves intact its ability to function as an inhibitory ligand for NK cells. Such genetically modified molecules may have potential therapeutic applications in the prevention of delayed xenograft rejection and in the facilitation of allogeneic and xenogeneic bone marrow engraftment. |
| Databáze: | OpenAIRE |
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