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.

Neonatal exposure to antigen primes the immune system to develop responses in various lymphoid organs and promotes bystander regulation of diverse T cell specificities.

Neonatal exposure to Ag has always been considered suppressive for immunity. Recent investigations, however, indicated that the neonatal immune system could be guided to develop immunity. For instance, delivery of a proteolipid protein (PLP) peptide on Ig boosts the neonatal immune system to develop responses upon challenge with the PLP peptide later.

TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs.

Ig-PLP1 and Ig-PLP-LR are chimeric Igs expressing proteolipid protein (PLP)-derived T cell agonist (PLP1) and antagonist (PLP-LR) peptides, respectively. Both chimeras, like free PLP1 and PLP-LR peptides, induce in vivo-specific T cell responses. However, the responses induced by Ig-PLP1 and Ig-PLP-LR were cross-reactive with both PLP1 and PLP-LR peptides, while those induced by free peptides were not.