GLYCANS AS TARGETS FOR MONOCLONAL-ANTIBODIES THAT PROTECT RATS AGAINST TRICHINELLA-SPIRALIS

GLYCANS AS TARGETS FOR MONOCLONAL-ANTIBODIES THAT PROTECT RATS AGAINST TRICHINELLA-SPIRALIS
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DOI:
10.1093/glycob/4.5.585
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发表时间:
1994-10-01
期刊:
影响因子:
4.3
通讯作者:
APPLETON, JA
APPLETON, JA
中科院分区:
生物学3区
文献类型:
--
作者:
ELLIS, LA;REASON, AJ;APPLETON, JA

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我们研究了旋毛虫抗原上聚糖在大鼠单克隆抗体(mAb)识别中的作用,这些抗体保护大鼠幼仔免受寄生虫的攻击。在感染母鼠所生的幼仔或用mAb被动免疫的幼仔中,抗体在数小时内从肠中消除攻击剂量(“快速排出”)。由于单克隆抗体可以提供如此显著的保护作用,我们试图表征它们靶向的寄生虫抗原。在这份报告中,我们表明,保护性抗体不能结合排泄/分泌(ES)抗原去糖基化与三氟甲磺酸(TFMS)。此外,通过碱性水解或肽:N糖苷酶F(PNGase F)消化从糖蛋白中分离的寡糖被保护性而非保护性mAb结合。用保护性mAb 9D亲和纯化的聚糖与除一种保护性mAb外的所有保护性mAb结合。这些抗体先前已显示与完整幼虫的表面结合,表明聚糖暴露在寄生虫表面。可能参与结合保护性mAb的候选聚糖具有不寻常的具有末端泰维糖部分的三触角和四触角结构(Reason等人,Glycobiology,4,000-000,1994)。用这种聚糖包被幼虫表面可用于保护寄生虫及其分泌产物在寄生虫行进并驻留在其上皮小生境中时免受酶攻击。
We have investigated the role of glycans on Trichinella spiralis antigens in recognition by rat monoclonal antibodies (mAbs) which protect rat pups against challenge with the parasite. In pups born to infected dams or pups passively immunized with mAbs, antibodies eliminate a challenge dose from the intestine within hours ((rapid expulsion'). Because such dramatic protection can be afforded by mAbs, we have sought to characterize the parasite antigens they target. In this report we show that protective antibodies were unable to bind excretory/secretory (ES) antigens deglycosylated with trifluoromethanesulphonic acid (TFMS). In addition, oligosaccharides isolated from glycoproteins by alkaline hydrolysis or peptide: N glycosidase F (PNGase F) digestion were bound by protective, but not non-protective, mAbs. Glycans affinity purified with protective mAb 9D bound to all but one protective mAb. These antibodies have been shown previously to bind to the surfaces of intact larvae, indicating that the glycan is exposed on the parasite surface. Candidate glycans that may be involved in binding protective mAbs have unusual tri- and tetra-antennary structures with terminal tyvelose moieties (Reason et al., Glycobiology, 4, 000-000, 1994). Coating of the larval surface with such glycans may serve to protect the parasite and its secreted products from enzymatic attack as the parasite travels to and resides in its epithelial niche.