Stimulatorische und inhibitorische Rezeptor/Ligand Interaktionen als Zielstrukturen für die Verminderung von humanen Immunantworten gegen porzines Xenoantigen

Analysis of SLA class-I expression in porcine tissues. Cryosections of heart, kidney, and liver from a wt pig and SLA class-I deficient (B2Mlow) pig 708/3 were stained with the anti-SLA class-I mAb 74-11-10. Antibody binding was detected by an HRPO-coupled secondary antibody and incubation with AEC. Nuclei were counterstained with hematoxylin. Magnification is x100. Hein, R., et al. Am J Transplant, 2019 Nov 15. doi: 10.1111/ajt.

The goal of this project is to establish conditions that elicit strong inhibitory and weak stimulatory signals in human immune cells when they interact with porcine tissues. Transgenic (tg) pigs expressing the human (h) inhibitory ligand hPD-L1 (CD274) and pigs lacking functional MHC (SLA, "swine leukocyte antigen") class I were generated. In vitro studies showed that SLA class I-deficient and hPD-L1 tg cells are only partially protected from human immune responses. We expect that hPD-L1 positive/SLA class I negative cells generated by combining both strategies will have extremely low immunogenicity. SLA-HLA typing and functional testing will identify SLA alleles with low stimulatory potential for the potential transplant recipient. Together with further "genetic engineering" in the context of ex vivo perfusion, it is thus possible to select or generate a xenograft tailored to the specific recipient ("personalized graft").

 

Team

Prof. Dr. Reinhard Schwinzer

 

 

Funding

SFB-TRR 127 Teilprojekt A1

 

Collaborations

We are working on the project together with Prof. Constanca Figueiredo (MHH, Dept. of Transfusion Medicine and Transplant Engineering).