Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues

Luca Inverardi, Barbara Clissi, Amy L. Stolzer, Jeffrey R. Bender, Mauro S. Sandrin, Ruggero Pardi

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

Background. In discordant xenogeneic species combinations, vascularized transplants are hyperacutely rejected, due to binding of xenoreactive natural antibodies (XNA) to selected tissues of the graft, followed by activation of the complement and coagulation cascades. A major epitope recognized by human XNA is the terminal disaccharide Galα(1,3)Gal. Poorly defined, early cell- mediated events also contribute to recognition and rejection of discordant xenografts, and we have suggested a role of natural killer (NK) lymphocytes in this process. Methods. Human NK cells were used as effectors in functional assays of adhesion to and lysis of xenogeneic discordant endothelial cells in vitro. Adhesion and lysis inhibition experiments were performed using a large panel of carbohydrates, as well as F(ab')2 fragments of human XNA. COS cells transduced with the porcine α-galactosyltransferase were also used as targets for NK cell adhesion. Results. We demonstrate that XNA-reactive carbohydrate epitopes expressed by xenogeneic cells, including Galα(1,3)Gal, are also directly recognized by human NK cells. First, selected carbohydrates in solution displace with comparable efficiency both XNA and NK cell binding to xenogeneic endothelium; second, XNA F(ab')2 fragments selectively inhibit human NK cell adhesion to porcine endothelium, but not to human endothelium; third, unstimulated NK lymphocytes adhere selectively to COS-7 cells expressing the porcine glycosyltransferase that encodes the Galα(1,3)Gal epitope. Conclusions. Collectively, our findings suggest that humoral and cellular components of the natural immune response against heterologous species independently evolved recognition patterns directed against overlapping carbohydrate determinants.

Original languageEnglish (US)
Pages (from-to)1318-1330
Number of pages13
JournalTransplantation
Volume63
Issue number9
DOIs
StatePublished - May 15 1997

ASJC Scopus subject areas

  • Transplantation

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