| 1. |
- Zhou, Dapeng, et al.
(författare)
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Lysosomal glycosphingolipid recognition by NKT cells.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 306:5702, s. 1786-9
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Tidskriftsartikel (refereegranskat)abstract
- NKT cells represent a distinct lineage of T cells that coexpress a conserved alphabeta T cell receptor (TCR) and natural killer (NK) receptors. Although the TCR of NKT cells is characteristically autoreactive to CD1d, a lipid-presenting molecule, endogenous ligands for these cells have not been identified. We show that a lysosomal glycosphingolipid of previously unknown function, isoglobotrihexosylceramide (iGb3), is recognized both by mouse and human NKT cells. Impaired generation of lysosomal iGb3 in mice lacking beta-hexosaminidase b results in severe NKT cell deficiency, suggesting that this lipid also mediates development of NKT cells in the mouse. We suggest that expression of iGb3 in peripheral tissues may be involved in controlling NKT cell responses to infections and malignancy and in autoimmunity.
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| 2. |
- Li, Yunsen, et al.
(författare)
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Sensitive detection of isoglobo and globo series tetraglycosylceramides in human thymus by ion trap mass spectrometry.
- 2008
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 18:2, s. 158-65
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Tidskriftsartikel (refereegranskat)abstract
- Glycosphingolipids serve as ligands for receptors involved in signal transduction and immune recognition, as exemplified by isoglobotrihexosylceramide, an antigenic ligand for T cell receptors. Mechanistic studies on the regulation of isoglobotrihexosylceramide require biochemical measurement of its lysosomal precursor, isoglobotetraglycosylceramide. It remains a challenge to distinguish between complex tetraglycosylceramide glycosphingolipid isomers with the same sugar components but diverse internal linkages. Here we established a simple and sensitive method to separate globo- and isoglobotetraglycosylceramide by MS5 ion trap mass spectrometry, and report the identification of isoglobotetraglycosylceramide in a CHO cell line transfected by iGb3 synthase, as well as in human thymus.
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| 3. |
- Liu, Qiyong P., et al.
(författare)
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Bacterial glycosidases for the production of universal red blood cells
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 25:4, s. 454-464
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Tidskriftsartikel (refereegranskat)abstract
- Enzymatic removal of blood group ABO antigens to develop universal red blood cells ( RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical practice has been the lack of efficient glycosidase enzymes. Here we report two bacterial glycosidase gene families that provide enzymes capable of efficient removal of A and B antigens at neutral pH with low consumption of recombinant enzymes. The crystal structure of a member of the alpha-N-acetylgalactosaminidase family reveals an unusual catalytic mechanism involving NAD(+). The enzymatic conversion processes we describe hold promise for achieving the goal of producing universal RBCs, which would improve the blood supply while enhancing the safety of clinical transfusions.
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| 4. |
- Liu, Qiyong P, et al.
(författare)
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Identification of a GH110 subfamily of alpha 1,3-galactosidases - Novel enzymes for removal of the alpha 3Gal xenotransplantation antigen
- 2008
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 283:13, s. 8545-8554
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Tidskriftsartikel (refereegranskat)abstract
- In search of alpha-galactosidases with improved kinetic properties for removal of the immunodominant alpha 1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of alpha-galactosidases (CAZy GH110) with highly restricted substrate specificity and neutral pH optimum (Liu, Q. P., Sulzenbacher, G., Yuan, H., Bennett, E. P., Pietz, G., Saunders, K., Spence, J., Nudelman, E., Levery, S. B., White, T., Neveu, J. M., Lane, W. S., Bourne, Y., Olsson, M. L., Henrissat, B., and Clausen, H. (2007) Nat. Biotechnol. 25, 454-464). One member of this family from Bacteroides fragilis had exquisite substrate specificity for the branched blood group B structure Gal alpha 1-3(Fuc alpha 1-2) Gal, whereas linear oligosaccharides terminated by alpha 1,3-linked galactose such as the immunodominant xenotransplantation epitope Gal alpha 1-3Gal beta 1-4GlcNAc did not serve as substrates. Here we demonstrate the existence of two distinct subfamilies of GH110 in B. fragilis and thetaiotaomicron strains. Members of one subfamily have exclusive specificity for the branched blood group B structures, whereas members of a newly identified subfamily represent linkage specific alpha 1,3-galactosidases that act equally well on both branched blood group B and linear alpha 1,3Gal structures. We determined by one-dimensional H-1 NMR spectroscopy that GH110 enzymes function with an inverting mechanism, which is in striking contrast to all other known alpha-galactosidases that use a retaining mechanism. The novel GH110 subfamily offers enzymes with highly improved performance in enzymatic removal of the immunodominant alpha 3Gal xenotransplantation epitope.
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| 5. |
- Zhou, Dapeng, et al.
(författare)
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Immunologic mapping of glycomes: implications for cancer diagnosis and therapy.
- 2011
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Ingår i: Frontiers in bioscience (Scholar edition). - 1945-0524. ; 3, s. 1520-32
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Tidskriftsartikel (refereegranskat)abstract
- Cancer associated glycoconjugates are important biomarkers, as exemplified by globo-H, CA125, CA15.3 and CA27.29. However, the exact chemical structures of many such biomarkers remain unknown because of technological limitations. In this article, we propose the "immunologic mapping" of cancer glycomes based on specific immune recognition of glycan structures, which can be hypothesized theoretically, produced chemically, and examined biologically by immuno-assays. Immunologic mapping of glycans not only provides a unique perspective on cancer glycomes, but also may lead to the invention of powerful reagents for diagnosis and therapy.
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