Immunomodulatory properties of a phosphorylcholine-containing secreted filarial glycoprotein

ES-62 is a phosphorylcholine (PC)-containing glycoprotein which is secreted by the rodent filarial nematode Acanthocheilonema viteae. A homologue exis ts in the human filarial nematode Brugia malayi and indeed PC is found atta ched to glycoproteins of many, if not all, filarial species. At concentrati ons equivalent to those found for PC-containing molecules in the bloodstrea m of parasitized humans, ES-62 is able to polyclonally activate certain pro tein tyrosine kinase and mitogen-activating protein kinase signal-transduct ion elements in B and T lymphocytes following in-vitro exposure. Although t his interaction is insufficient to cause lymphocyte proliferation per se, i t serves to desensitize the cells to subsequent activation of the phosphoin ositide-3-kinase, protein kinase C and Ras mitogen-activating protein kinas e pathways and hence also to proliferation via the antigen receptors. The a ctive component of ES-62 appears to be PC, as the results obtained with ES- 62 are broadly mimicked by PC conjugated to BSA or PC alone. Although PC ca n also be shown to desensitize B cells following in-vivo administration, no t all cells are affected, as it is still possible to generate an antibody r esponse. Dissection of this response indicates that it is of the Th2 type.