Genetically modified HLA class I molecules able to inhibit human NK cells without provoking alloreactive CD8+ CTLs.

Human NK cells are likely to be important effectors of xenograft rejection. Expression of HLA class I molecules by transfected porcine cells can protect them from human NK cell-mediated lysis; however, this strategy has the potential to augment the anti-graft response by recipient CD8(+) T cells recognizing foreign pig peptides presented by HLA. In this study we show that the introduction of a mutation (D227K) in the alpha(3) domain of HLA-Cw3 abrogates its recognition by CD8-dependent T cells but leaves intact its ability to function as an inhibitory ligand for NK cells.