Characterization of two monoclonal antibodies raised in Btk^xid mice that recognize phosphorylcholine‐bearing antigens from Trichinella and other helminths

Abstract

This study investigated the binding properties of two monoclonal antibodies (mAbs US1 and US2) raised in (CBA/n x BALB/c)F1 (NBF1) Btk(xid) male mice. Both mAbs show unusual specificity for phosphorylcholine (PC)-containing TSL4 antigens of Trichinella. Specifically, and in contrast to mAbs raised in normal mice, US1 and US2 mAbs do not bind to artificial PC-protein conjugates and are not inhibited by either free PC or NPPC, although US2 was partially inhibited by NPPC at high concentration (10(-2) M). However, both mAbs completely abrogate the binding to Trichinella antigens of other anti-PC mAbs (e.g. BH8 and Mab-2). These results suggest that both US1 and US2 recognize complex PC-containing epitopes. The patterns of recognition of PC-bearing antigens from different helminths by US1, US2, Mab-2 and BH8 were broadly correlated with phylogenetic proximity. The closest similarities were observed between the members of the Trichinelloidea superfamily (Trichinella spiralis and Trichuris muris) and among the ascarids (Toxocara canis, Anisakis simplex, Hysterothylacium aduncum and Ascaris lumbricoides). However, US1 did not react with the filarial nematode Onchocerca volvulus and reacted only weakly with Onchocerca gibsoni, while US2 reacted only weakly with both species. Only BH8 recognized PC-bearing antigens from the trematode Fasciola hepatica and the cestode Bothriocephalus scorpii. These results suggest that PC is attached to identical or very similar structures on most different nematode species, although major differences exist with respect to helminth species from groups such as the trematodes and cestodes that are phylogenetically distant from the nematodes.

Evaluation ofTrichinella spiralisLarva Group 1 Antigens for Serodiagnosis of Human Trichinellosis

“…The low specificity of Trichinella CLE preparations for diagnosis of human trichinellosis has been reported previously (28,44); however, it is believed that CLE preparations may be useful for early detection of Trichinella infections (28,41,44). Although it is expected that some of the antigens contained in CLE preparations may be recognized earlier than TSL-1 antigens, the data presented here suggest that such CLE antigens either are not specific (e.g., phosphorylcholine) (18,40) or have immunogenicity below the threshold of the response induced by immunodominant cross-reactive antigens.…”

Antibody responses to Ascaris‐derived proteins and glycolipids: the role of phosphorylcholine

“…Interestingly, the responses to Ascaris glycolipids could be partially inhibited by competition with free PC, but almost completely by HF treatment. This difference might be accounted for by the fact that some antibodies will recognize only the PC moiety and can bind free PC, whereas other antibodies that bind to PC, do so in the context of structures that it is attached to, and therefore will not be competed away by free PC alone (35). The possibility that HF treatment destroys glycolipids was ruled out not only by mass spectrometry, but also functionally by showing intact binding of monoclonal antibodies to LacdiNAc (GalNAc(β1‐4)GlcNAcβ1‐) structures present on glycolipids of Ascaris both before and after treatment with HF (data not shown).…”

CD36 and Platelet-Activating Factor Receptor Promote House Dust Mite Allergy Development

“…Based on these observations, we investigated whether HDM allergy development depended on CD36 or PAFR and whether engagement of these receptors on epithelial or dendritic cells in the lung is involved in HDM-induced allergic disease. Induced or passively administered anti-PC IgM antibodies are protective in disease models involving PC-expressing bacteria, parasites, apoptotic cells, and metabolic products (34–39). Similarly, we have shown that increased anti-PC IgM levels in serum and lungs are associated with suppressed allergy development (22).…”