TISSUE SPECIFIC RECOGNITION IN HUMAN ANTI-PORCINE RESPONSE INDICATES PEPTIDE SPECIFICITY IN XENORECOGNITION.

Abstract

519 MHC molecules play critical roles in both allo- and xeno-responses. However, the role of xeno-MHC bound peptides is poorly understood. The human anti-porcine response is of particular interest because of the potential clinical use of porcine organs in human transplantation. Our previous data have shown that acid treatment of porcine target cells, which deprived the porcine MHC (SLA) of its associated peptide, significantly reduced the lysis by SLA allele restricted CTL. This reduction in CTL lysis can be restored by providing relevant peptides, suggesting that human anti-porcine xenorecognition is peptide dependent. In this study, to further characterize the peptide specificity in human anti-porcine xenorecognition, we generated CD8+ T cell clones from an established human anti-porcine aortic endothelial cell CTL line. A majority of the clones (89%) recognized both the porcine endothelial cells and lymphoblastoid cells from the same pig. However, a portion of the CTL clones (11%) only recognized the porcine endothelial cells, suggesting that these T cell clones recognize endothelial tissue antigen in the context of SLA class I molecules. Following transfection of a restricted SLA class I gene into both porcine and human cell lines, we found that a majority of the T cell clones (54%) lysed the SLA allele transfected into both pig and human cells. Again, a portion of the T cell clones (8%) only recognized the SLA expressed on porcine cells. These data indicate that a significant part of the human anti-porcine xenorecognition is not only peptide dependent, but also peptide sequence restricted. This strongly suggests that peptide specificity may play an important role in human anti-porcine xenorecognition.