The alloimmune response to human induced pluripotent stem cells and their differentiated progeny in a humanised mouse model. (360G-Wellcome-100053_Z_12_Z)

Human induced pluripotent stem cells (hiPSCs) generated from adult cells such as skin fibroblast have the ability to differentiate into many cell types including pancreatic progenitor cells. Humanised mice reconstituted with a human immune compartment are an invaluable tool in the study of the humoral alloimmune response to hiPSCs and their differentiated progeny. This alloimmune response is, however, not yet characterized but is likely to be determined in large part by HLA expression. My projec t aims to first characterize the immune response to human adult or hiPSC-derived cells in a humanised mouse model by addressing the hypothesis that optimal humoral alloimmunity requires positive thymic selection of CD4 T cells on human MHC. Next, hiPSCs will be derived from skin fibroblasts and differentiated into pancreatic progenitors. The humoral immune response to autologous or allogeneic hiPSC-derived pancreatic progenitor cells will be compared in humanised mice with the response against a dult islets, to test the hypothesis that HLA class I expression by hiPSCs increases after differentiation but that the humoral alloimmune response is nonetheless dampened compared to the response against adult cells.