SUPPRESSION OF ALLOGENEIC REACTIVITY IN-VITRO BY THE SYNCYTIOTROPHOBLAST MEMBRANE GLYCOCALYX OF THE HUMAN TERM PLACENTA IS CARBOHYDRATE DEPENDENT

Immunosuppressive factors isolated from trophoblast are known to block both innate and major histocompatability complex (MHC)-dependent cell -mediated immune responses in vitro and, in some cases, in vivo. We in vestigated the biochemical nature of these factors, which is presently unknown. Immunosuppressive activity, assessed by inhibition of two-wa y MLR, was extracted from term syncytiotrophoblast microvilli using 3 M KCl. The activity resisted both extensive pronase digestion and heat ing to 90 degrees C for 1 h, demonstrating that intact membrane protei ns were not required. Although purified protein-linked oligosaccharide s released by hydrazinolysis from the syncytiotrophoblast membrane wer e themselves inactive, they blocked the immunosuppressive activity of the KCl extract. After pronase digestion, the activity could be fracti onated by TSK 55S gel filtration, followed by C18 reverse-phase chroma tography. Sequential exoglycosidase digestion of hydrazine-released su gars of the active fraction demonstrated that it contained neutral N-l inked oligomannose and hybrid oligosaccharides, which normally make up <3% of the total syncytiotrophoblast-derived protein glycan library. These glycopeptides of the active fraction were associated with membra ne phospholipid micelles. The possible mechanism by which incompletely processed N-linked oligosaccharides expressed by a variety of syncyti otrophoblast membrane glycoproteins may block allogeneic reactivity wh en presented as polyvalent sugar groups is discussed.