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 exists in the human filarial nematode Brugia malayi and indeed PC is found attached to glycoproteins of many, if not all, filarial species. At concentrations equivalent to those found for PC-containing molecules in the bloodstream of parasitized humans, ES-62 is able to polyclonally activate certain protein tyrosine kinase and mitogen-activating protein kinase signal-transduction elements in B and T lymphocytes following in-vitro exposure. Although this interaction is insufficient to cause lymphocyte proliferation per se, it serves to desensitize the cells to subsequent activation of the phosphoinositide-3-kinase, protein kinase C and Ras mitogen-activating protein kinase pathways and hence also to proliferation via the antigen receptors. The active 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 can also be shown to desensitize B cells following in-vivo administration, not all cells are affected, as it is still possible to generate an antibody response. Dissection of this response indicates that it is of the Th2 type.
Harnett
W
W
Department of Immunology, University of Strathclyde, Glasgow G4 ONR, UK.
Deehan
M R
MR
Houston
K M
KM
Harnett
M M
MM
D000818:Animals; D000909:Antibodies, Helminth / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D004153:Dipetalonema / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010767:Phosphorylcholine / Q000032:analysis; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D000909:Antibodies, Helminth; D006023:Glycoproteins; D015801:Helminth Proteins; D010767:Phosphorylcholine; D015847:Interleukin-4; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D018631:ras Proteins