Adaptive Immune Activation: Glycosylation Does Matter

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2013 Nov 16

PMID 24231619

Citations 144

Authors

Margreet A Wolfert

Geert-Jan Boons

Affiliations

Soon will be listed here.

Abstract

Major histocompatibility complex (MHC) class I and II are glycoproteins that can present antigenic peptides at the cell surface for recognition and activation of circulating T lymphocytes. Here, the importance of the modification of protein antigens by glycans on cellular uptake, proteolytic processing, presentation by MHC and subsequent T-cell priming is reviewed. Antigen glycosylation is important for a number of diseases and vaccine design. All of the key proteins involved in antigen recognition and the orchestration of downstream effector functions are glycosylated. The influence of protein glycosylation on immune function and disease is covered.

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References

Altrich-Vanlith M, Ostankovitch M, Polefrone J, Mosse C, Shabanowitz J, Hunt D . Processing of a class I-restricted epitope from tyrosinase requires peptide N-glycanase and the cooperative action of endoplasmic reticulum aminopeptidase 1 and cytosolic proteases. J Immunol. 2006; 177(8):5440-50. DOI: 10.4049/jimmunol.177.8.5440. View

Chen I, Chen H, Demetriou M . Lateral compartmentalization of T cell receptor versus CD45 by galectin-N-glycan binding and microfilaments coordinate basal and activation signaling. J Biol Chem. 2007; 282(48):35361-72. DOI: 10.1074/jbc.M706923200. View

Plato A, Willment J, Brown G . C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways. Int Rev Immunol. 2013; 32(2):134-56. PMC: 3634610. DOI: 10.3109/08830185.2013.777065. View

Perillo N, Pace K, Seilhamer J, Baum L . Apoptosis of T cells mediated by galectin-1. Nature. 1995; 378(6558):736-9. DOI: 10.1038/378736a0. View

Rillahan C, Paulson J . Glycan microarrays for decoding the glycome. Annu Rev Biochem. 2011; 80:797-823. PMC: 3116967. DOI: 10.1146/annurev-biochem-061809-152236. View

Pilobello K, Mahal L . Deciphering the glycocode: the complexity and analytical challenge of glycomics. Curr Opin Chem Biol. 2007; 11(3):300-5. DOI: 10.1016/j.cbpa.2007.05.002. View

Sancho D, Reis e Sousa C . Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol. 2012; 30:491-529. PMC: 4480235. DOI: 10.1146/annurev-immunol-031210-101352. View

Jensen T, Hansen P, Galli-Stampino L, Mouritsen S, Frische K, Meinjohanns E . Carbohydrate and peptide specificity of MHC class II-restricted T cell hybridomas raised against an O-glycosylated self peptide. J Immunol. 1997; 158(8):3769-78. View

Buskas T, Ingale S, Boons G . Glycopeptides as versatile tools for glycobiology. Glycobiology. 2006; 16(8):113R-136R. DOI: 10.1093/glycob/cwj125. View

10.

Batista F, Harwood N . The who, how and where of antigen presentation to B cells. Nat Rev Immunol. 2008; 9(1):15-27. DOI: 10.1038/nri2454. View

11.

Dam T, Brewer C . Lectins as pattern recognition molecules: the effects of epitope density in innate immunity. Glycobiology. 2009; 20(3):270-9. DOI: 10.1093/glycob/cwp186. View

12.

Marth J, Grewal P . Mammalian glycosylation in immunity. Nat Rev Immunol. 2008; 8(11):874-87. PMC: 2768770. DOI: 10.1038/nri2417. View

13.

Steentoft C, Vakhrushev S, Vester-Christensen M, Schjoldager K, Kong Y, Bennett E . Mining the O-glycoproteome using zinc-finger nuclease-glycoengineered SimpleCell lines. Nat Methods. 2011; 8(11):977-82. DOI: 10.1038/nmeth.1731. View

14.

Johnson M, Bundle D . Designing a new antifungal glycoconjugate vaccine. Chem Soc Rev. 2012; 42(10):4327-44. DOI: 10.1039/c2cs35382b. View

15.

Hanisch F, Ninkovic T . Immunology of O-glycosylated proteins: approaches to the design of a MUC1 glycopeptide-based tumor vaccine. Curr Protein Pept Sci. 2006; 7(4):307-15. DOI: 10.2174/138920306778018034. View

16.

Gaidzik N, Westerlind U, Kunz H . The development of synthetic antitumour vaccines from mucin glycopeptide antigens. Chem Soc Rev. 2013; 42(10):4421-42. DOI: 10.1039/c3cs35470a. View

17.

Beatson R, Taylor-Papadimitriou J, Burchell J . MUC1 immunotherapy. Immunotherapy. 2010; 2(3):305-27. DOI: 10.2217/imt.10.17. View

18.

Hsu D, Chen H, Liu F . Galectin-3 regulates T-cell functions. Immunol Rev. 2009; 230(1):114-27. DOI: 10.1111/j.1600-065X.2009.00798.x. View

19.

Werdelin O, Meldal M, Jensen T . Processing of glycans on glycoprotein and glycopeptide antigens in antigen-presenting cells. Proc Natl Acad Sci U S A. 2002; 99(15):9611-3. PMC: 124945. DOI: 10.1073/pnas.152345899. View

20.

Lizak C, Gerber S, Numao S, Aebi M, Locher K . X-ray structure of a bacterial oligosaccharyltransferase. Nature. 2011; 474(7351):350-5. DOI: 10.1038/nature10151. View