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home >   personnel > » Prof. Fran M. Platt » Celeste Chuang » Dr. Emyr Lloyd-Evans » Ksenia Peterneva » Dr. David A. Priestman » Viv Reeve » Dave Smith » Dr. Annie Speak » Danielle Taylor-te Vruchte » Dr. Kerri-Lee Wallom » Dr. Ian Williams » Oscar Chen lab alumni > » Dr. Aarnoud van der Spoel » Dr. Barry Boland » Dr. Jey M. Jeyakumar   research areas > »Disorders of glyco... »Glyco... in male reprod... »Glyco... in the immune s..   publications » » Recent publications » Featured publications » Platt Lab publication list   funding » » click for info   accessibility statement »

3. Glycosphingolipids in the immune system < back to research areas Summary The CD1 proteins are a family of MHC-like molecules that can present foreign and self lipids (including GSLs) within the immune system. We are particularly interested in CD1d molecules that present lipids to natural killer T cells. These cells express an invariant TCR alpha chain and respond rapidly when they recognise antigen presented by CD1d. We are interested in the nature of endogenous GSL ligands in thymic selection and peripheral activation. A second recent area of interest is in GSLs as targets in autoimmune diseases, particularly in the autoimmune neuropathies of the peripheral nervous system (e.g. Guillain Barré syndromes). Recent Findings Found no evidence to support iGb3 being a thymic selecting ligand for iNKT cell development in mouse and man (Fig 1). Dr. Annie Speak Fig. 1 NP-HPLC profile of mouse, human and rat thymus neutral GSL-derived oligosaccharides. Mouse and human profiles are representative of three independent experiments and the rat profile is representative of four independent experiments. Dotted lines indicate the elution time of iGb3 and iGb4 standards. α-gala-/- aged 38 wks and, hexb-/- and control aged 9 wks. The insets show the profiles scaled to that of the rat thymus where iGb3 is detectable. Have identified charged glycosphingolipids as potential peripheral iNKT cell activating ligands in response to TLR9 ligands.   Dr. Annie Speak We have proof of principle that GSL depletion using the drug miglustat (NB-DNJ) protects from autoimmune mediated toxicity in cultured cells. Kerri-Lee Wallom Ongoing studies Determine the biochemical nature of thymic and peripheral iNKT cell ligands  Dr. Annie Speak Perform in vivo studies to test the therapeutic potential of GSL depletion in autoimmune neuropathies Dr. Kerri-Lee Wallom   Refs  Speak, AO, Salio, M., Neville, DC, Fontaine, J., Priestman, DA, Platt, N., Heare, T., Butters, TD, Dwek, RA, Trottein, F., Exley, MA, Cerundolo, V. and Platt FM (2007). Implications for CD1d restricted NKT cell ligands by the restricted presence of isoglobotrihexosylceramide (iGb3) in mammals. Proc. Natl. Acad. Sci. U.S.A. 104, 5971-5976   Porubsky, S., Speak, A.O., Lucklow, B., Cerundolo, V., Platt, F.M. and Grone, H-J. (2007) Normal development and function of iNKT cells in mice deficient in isoglobotrihexosylceramide (iGb3). Proc. Natl. Acad. Sci. U.S.A. 104, 5977-5982 Padget, C, Speak, A.O., Mallevaey, T., Torres, D., Fontaine, J., Ryffel, B., Capron, M., Sheehan, K.C.F., Faveeuw, C., de Moraes, M.L., Platt, F.M. and Trottein, F. (2007). Activation of invariant NKT cells by CpG ODN-stimulated myeloid dendritic cells requires IFN-b and de novo synthesis of charged b-linked glycosphingolipids. Immunity, 27, 1-13 Sallio, M., Speak, A.O., Shepherd, D., Polzella, P., Illarionov, P.,Veerapen, N., Besra, GS, Platt FM and Cerundolo, V. (2007) Modulation of human natural killer T cell ligands on TLR-mediated antigen–presenting cell activation.      Proc. Natl. Acad. Sci (USA), 104, 20490-20495 < to top