The Role of NK Cells in Pig-to-Human Xenotransplantation

Figure 2

NK cell-mediated destruction of pig endothelial cells by recognition of human anti-pig antibodies (ADCC). Preformed natural XenoAbs circulating in the blood, mainly directed against αGal but also other sugar antigens such as Neu5Gc, bind to pig endothelial cells with their Fab portion. The Fc-fractions of the antibodies are recognized by the FcRs located on the surface of NK cells, for instance, CD16 (FcγRIIIa) triggering the signaling cascade that leads to NK cell degranulation. The release of their lytic granules containing granzymes and perforin leads to target cell destruction, in this particular context, pig endothelial cells lysis, a process known as antibody-dependent cell-mediated cytotoxicity (ADCC). Alternatively, induced anti-SLA class I antibodies (far right) are recognized by NK cells via CD16, also leading to ADCC. αGal: alpha Gal xenoantigen; HD Ag: Hanganutziu-Deicher antigen; Neu5Gc, SLA-I: swine leukocyte antigen class I.