A1: Targeting stimulatory and inhibitory receptor/ligand interactions to diminish human anti-pig immune responses

It is the aim of this project to establish conditions leading to strong inhibitory and weak stimulatory signals in human immune cells when they come into contact with porcine cells and tissues. To enhance inhibitory signals, pigs over-expressing the human inhibitory ligand PD-L1 have been generated. Human immune responses to cells and tissues from these pigs will be assessed. Stimulatory signals will be reduced by decreasing the expression level (RNA interference) of pig MHC/SLA molecules which are major stimulators for human T cells. We expect a particularly low immunogenicity of porcine cells and tissues expressing a PD-L1high SLAlow phenotype.