Phosphorylcholine

Haptens, a special class of antigen, are small molecules that induce specific antibody production when they are attached to a protein that acts as a carrier. Phosphorylcholine is one such hapten that has been widely used in the investigation of immune responses. The specific binding of this hapten... 

Satow, Y., et al. Phosphorylcholine-binding immunoglobulin Fab McPC603. An x-ray diffraction study at 2.7 A. 

Segal, D.M., et al. The three-dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen-binding site. Proc. Natl. Acad. Sci. USA 71 4298-4302, 1974. 

A ubiquitous phospholipid mediator (acetyl-glyceryl-ether-phosphorylcholine) in inflammation. Among others, it stimulates platelet aggregation and causes swelling, smooth contraction or dilation and neutrophil activation. 

Biomembranes mainly consists of phospholipid matrices, and the major component is phosphorylcholines (PC). PC is an amphiphile consisting of hydrophilic headgroup and hydrophobic long chains. In view of the amphiphilic feature of PC, we can divide hydrated lipid bilayers into the three zones, I, II, and III. The zone model, which has been used in a recent NMR study of DD [46-48], is illustrated in Fig. 2. 

Denkers, E.Y., Wassom, D.L. and Flayes, C.E. (1990a) Characterization of Trichinella spiralis antigens sharing an immunodominant, carbohydrate-associated determinant distinct from phosphorylcholine. Molecular and Biochemical Parasitology 41, 241-249. 

Sanmartin, M.L., Iglesias, R., Santamarina, M.T., Leiro,J. and Ubeira, F.M. (1991) Anatomical location of phosphorylcholine and other antigens on encysted TrichineUa using immunohistochemistry followed by Wheadey s trichrome stain. Parasitology Research 77, 301-306. 

Harnett, W., Houston, KM., Amess, R. and Worms, M.J. (1993) Acanthocheilonema viteae. phosphorylcholine is attached to the major excretory-secretory product via a N-linked glycan. Experimental Parasitology 77, 498-502. 

Haslam, S.M., Khoo, K-H., Houston, K.M., Harnett, W., Morris, H.R. and Dell, A. (1997) Characterisation of the phosphorylcholine-containing A-linked oligosaccharides in the excretory-secretory 62 kDa glycoprotein of Acanthocheilonema viteae. Molecular and Biochemical Parasitology 85, 53—66. 

Houston, K.M., Cushley, W.C. and Harnett, W. (1997) Studies on the site and mechanism of attachment of phosphorylcholine to a filarial excretory-secretory product. Journal of Biological Chemistry 272, 1527-1533. 

Maizels, R.M., Burke, L. and Denham, D.A. (1987c) Phosphorylcholine-bearing antigens in filarial nematode parasites analysis of somatic extracts, in-vitro secretions and infection sera from Brugia malayi and B. pahangi. Parasite Immunology 9, 49-66. 

Fig. 19.1. Structure of phosphorylcholine (PC). PC is involved in phosphodiester linkage to carbohydrate in a number of lower organisms, including filarial nematodes (linking sugar appears to be A/-acetylglucosamine on species examined to date).

AlQaoud, KM., Fleischer, B. and Hoerauf, A. (1998) The Xid defect imparts susceptibility to experimental murine filariasis - association with a lack of antibody and IL-10 production by B cells in response to phosphorylcholine. International Immunology 10, 17—25. 

Bach, M.A, Kohler, H. and Levitt, D. (1983) Binding of phosphorylcholine by non-immunoglobulin molecules on mouse B cells. Journal of Immunology 131, 365-371. 

Beckmann, E. and Levitt, D. (1984) Phosphorylcholine on Streptococcus pneumoniae R36a is responsible for in vitro polyclonal antibody secretion by human peripheral blood lymphocytes. Journal of Immunology 132, 2174-2176. 

Deehan, M.R., Frame, M.J., Parkhouse, R.M., Seatter, S.D., Reid, S.D., Harnett, M.M. and Harnett, W. (1998) A phosphorylcholine-containing filarial nematode-secreted product disrupts B lymphocyte activation by targeting key proliferative signaling pathways. Journal of Immunology 160, 2692-2699. 

Gerdt, S., Dennis, R.D., Borgonie, G., Schnabel, R. and Geyer, R. (1999) Isolation, characterization and immunolocalization of phosphorylcholine-substituted glycolipids in developmental stages of Caenorhabditis elegans. European Journal of Biochemistry 266, 952—963. 

Harnett, W. and Harnett, M.M. (1993) Inhibition of murine B cell proliferation and down-regulation of protein kinase C levels by a phosphorylcholine-containing filarial excretory-secretory product. Journal of Immunology 151, 4829-4837. 

Houston, KM. and Harnett, W. (1999b) Mechanisms underlying the transfer of phosphorylcholine to filarial nematode glycoproteins - a possible role for choline kinase. Parasitology 118, 311-318. 

Jimenez, B., del Peso, L., Montaner, S., Esteve, P. and Lacal,J.C. (1995) Generation of phosphorylcholine as an essential event in the activation of Raf-1 and MAP-kinases in growth factors-induced mitogenic stimulation. Journal of Cellular Biochemistry 57, 141—149. 

Lai, R.B., Kumaraswami, V., Steel, C. and Nutman, T.B. (1990) Phosphorylcholine-containing antigens of Brugia malayi non-specifically suppress lymphocyte function. American Journal of Tropical Medicine and Hygiene 42, 56-64. 

Mitchell, G.F. and Lewers, H.M. (1976) Studies on immune responses to parasite antigens in mice IV. Inhibition of an anti-DNP antibody response with antigen, DNP-Ficoll containing phosphorylcholine. International Archives of Allergy and Applied Immunology 52, 235—240. 

Trolle, S., Andremont, A. and Fattal, E. (1998) Towards a multipurpose mucosal vaccine using phosphorylcholine as an unique antigen STP Pharmasciences 8, 19-30. 

---