Bee Venom Phospholipase A2, a Good -Chauffeur- for Delivering Tumor Antigen to the MHC I and MHC II Peptide-Loading Compartments of the Dendritic Cells: The Case of NY-ESO-1Reportar como inadecuado




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Bee venom phospholipase A2 bvPLA2 is a small, 15kDa enzyme which hydrolyses many phospholipids through interfacial binding. The mutated bvPLA2H34Q bvPLA2m, in which histidine-34 is replaced by glutamine, is not catalytically active. This protein has been shown to be a suitable membrane anchor and has been suggested as a suitable tumor-antigen vector for the development of novel dendritic cell-based vaccines. To confirm this feature, in this study the fusion protein PNY, composed of NY-ESO-1NYs fused to the C-terminus of bvPLA2m, was engineered. bvPLA2m enhanced the binding of NYs to the membrane of human monocyte-derived dendritic cells DCs and, once taken up by the cells, the antigen fused to the vector was directed to both MHC I and MHC II peptide-loading compartments. bvPLA2m was shown to increase the cross-presentation of the NYs-derived, restricted HLA-A*02 peptide, NY-ESO-1157-165NY157-165, at the T1 cell surface. DCs loaded with the fusion protein induced cross-priming of NYs-specific CD8 + T-cells with greater efficiency than DCs loaded with NYs. Sixty-five percent of these NYs-specific CD8+ T-cell lines could also be activated with the DCs pulsed with the peptide, NY157-165. Of these CD8+ T-cell lines, two were able to recognize the human melanoma cell line, SK-MEL-37, in a context of HLA-A*02. Only a small number of bvPLA2m CD8+ T-cell lines were induced, indicating the low immunogenicity of the protein. It was concluded that bvPLA2m can be used as a membrane-binding vector to promote MHC class II peptide presentation and MHC class I peptide cross-presentation. Such a system can, therefore, be tested for the preparation of cell-based vaccines.



Autor: Christine Almunia , Marie Bretaudeau, Gerhard Held, Aurélie Babon, Charles Marchetti, Florence Anne Castelli, André Ménez, Ber

Fuente: http://plos.srce.hr/



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