アクティブボード・２００８年１１月
　　　　　・・・・・２００８年１１月　４日更新・・・・・

研究発表を行った学会；
・The 10th International Symposium on Dendritic Cells.
　２００８年１０月１日～５日(神戸)

タイトル；Activation of antigen-specific cytotoxic T lymphocytes by β2-microglobulin or TAP1 gene disruption and the introduction of recipient-matched MHC class I gene in allogeneic ES cell-derived dendritic cells.
　
発表者；　松永　雄亮　氏
　　　（熊本大学　大学院医学教育部　免疫識別学分野）
Abstract；
　A method for the genetic modification of dendritic cells (DC) was previously established based on the in vitro differentiation of embryonic stem (ES) cells to DC (ES-DC). The unavailability of human ES cells genetically identical to the patients will be a problem in the future clinical application of this technology. This study attempted to establish a strategy to overcome this issue. The TAP1 or β2-microglobulin (β2m) gene was disrupted in 129 (H-2b)-derived ES cells and then expression vectors for the H-2Kd or β2m-linked form of Kd (β2m-Kd) were introduced, thus resulting in two types of genetically engineered ES-DC, TAP1-/-/Kd ES-DCand β2m-/-/β2m-Kd ES-DC. As intended, both of the transfectant ES-DC expressed Kd but not the intrinsic H-2b haplotype-derived MHC class I. β2m-/-/β2m-Kd and TAP1-/-/Kd ES-DC were not recognized by pre-activated H-2b-reactive CTL and did not prime H-2b reactive CTL in vitro or in vivo. β2m-/-/β2m-Kd ES-DC and TAP1-/-/Kd ES-DC had a survival advantage in comparison to β2m+/-/β2m-Kd ES-DC and TAP1+/+/Kd ES-DC, when transferred into BALB/c mice. Kd-restricted RSV-M2-derived peptide-loaded ES-DC could prime the epitope-specific CTL upon injection into the BALB/c mice, irrespective of the cell surface expression of intrinsic H-2b haplotype-encoded MHC class I. β2m-/-/β2m-Kd ES-DC were significantly more efficient in eliciting immunity against RSV M2 protein-expressing tumor cells than β2m+/-/β2m-Kd ES-DC. The modification of the β2m or TAP gene may therefore be an effective strategy to resolve the problem of HLA class I allele mismatch between human ES or induced pluripotent stem cells and the recipients to be treated.