Suppression of allogeneic reactivity in vitm by the syncytiotrophoblast membrane glycocalyx of the human term placenta is carbohydrate dependent

Immunosuppressive factors isolated from trophoblast are knownto block both innate and major histocompatability complex (MHC)-dependentcell-mediated immune responses in vitro and, in some cases,in vivo. We investigated the biochemical nature of these factors,which is presently unknown. Immunosuppressive activity, assessedby inhibition of two-way MLR, was extracted from term syncytiotrophoblastmicrovilli using 3 M KCl. The activity resisted both extensivepronase digestion and heating to 90°C for 1 h, demonstratingthat intact membrane proteins were not required. Although purifiedprotein-linked oligosaccharides released by hydrazinolysis fromthe syncytiotrophoblast membrane were themselves inactive, theyblocked the immunosuppressive activity of the KCl extract. Afterpronase digestion, the activity could be fractionated by TSK55S gel filtration, followed by C18 reverse-phase chromatography.Sequential exoglycosidase digestion of hydrazine-released sugarsof the active fraction demonstrated that it contained neutralN-linked oligomannose and hybrid oligosaccharides, which normallymake up <3% of the total syncytiotrophoblast-derived proteinglycan Library. These glycopeptides of the active fraction wereassociated with membrane phospholipid micelles. The possiblemechanism by which incompletely processed N-linked oligosaccharidesexpressed by a variety of syncytiotrophoblast membrane glycoproteinsmay block allogeneic reactivity when presented as polyvalentsugar groups is discussed. glycoprotein immunosuppression oligosaccharides pregnancy trophoblast