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Science 23 March 2001:
Vol. 291. no. 5512, pp. 2370 - 2376
DOI: 10.1126/science.291.5512.2370
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Review

Glycosylation and the Immune System

Pauline M. Rudd,1* Tim Elliott,2 Peter Cresswell,3 Ian A. Wilson,4 Raymond A. Dwek1*

Almost all of the key molecules involved in the innate and adaptive immune response are glycoproteins. In the cellular immune system, specific glycoforms are involved in the folding, quality control, and assembly of peptide-loaded major histocompatibility complex (MHC) antigens and the T cell receptor complex. Although some glycopeptide antigens are presented by the MHC, the generation of peptide antigens from glycoproteins may require enzymatic removal of sugars before the protein can be cleaved. Oligosaccharides attached to glycoproteins in the junction between T cells and antigen-presenting cells help to orient binding faces, provide protease protection, and restrict nonspecific lateral protein-protein interactions. In the humoral immune system, all of the immunoglobulins and most of the complement components are glycosylated. Although a major function for sugars is to contribute to the stability of the proteins to which they are attached, specific glycoforms are involved in recognition events. For example, in rheumatoid arthritis, an autoimmune disease, agalactosylated glycoforms of aggregated immunoglobulin G may induce association with the mannose-binding lectin and contribute to the pathology.

1 The Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
2 Cancer Sciences Division, University of Southampton Medical School, CRC Medical Oncology Unit, Level F, Centre Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
3 Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA.
4 Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
*   To whom correspondence should be addressed. E-mail: pmr{at}glycob.ox.ac.uk (P.M.R.) and raymond.dwek{at}exeter.oxford.ac.uk (R.A.D.)

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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