Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O-glycosylation, although different for MUC1 and IgA1, include dysregulation in glycosyltransferase expression, stability, and/or intracellular localization. Moreover, these aberrant glycoproteins are recognized by antibodies, although with different consequences. In breast cancer, elevated levels of antibodies recognizing aberrant MUC1 are associated with better outcome, whereas in IgA nephropathy, the antibodies recognizing aberrant IgA1 are part of the pathogenetic process.

Department of Immunology Faculty of Medicine and Dentistry Palacky University Hněvotínská 3 77515 Olomouc Czech Republic

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Brockhausen I. Mucin-type O-glycans in human colon and breast cancer: glycodynamics and functions. EMBO Rep. 2006;7:599–604. doi: 10.1038/sj.embor.7400705. PubMed DOI PMC

Chui D, et al. Genetic remodeling of protein glycosylation in vivo induces autoimmune disease. Proc Natl Acad Sci USA. 2001;98:1142–1147. doi: 10.1073/pnas.98.3.1142. PubMed DOI PMC

Kobata A. A retrospective and prospective view of glycopathology. Glycoconj J. 1998;15:323–331. doi: 10.1023/A:1006961532182. PubMed DOI

Rudd PM, Elliott T, Cresswell P, Wilson IA, Dwek RA. Glycosylation and the immune system. Science. 2001;291:2370–2376. doi: 10.1126/science.291.5512.2370. PubMed DOI

Ju T, Cummings RD. Protein glycosylation: chaperone mutation in Tn syndrome. Nature. 2005;437:1252. doi: 10.1038/4371252a. PubMed DOI

Tabak LA. The role of mucin-type O-glycans in eukaryotic development. Semin Cell Dev Biol. 2010;6:616–621. PubMed PMC

Tomana M, et al. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J Clin Invest. 1999;104:73–81. doi: 10.1172/JCI5535. PubMed DOI PMC

Suzuki H, et al. IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Invest. 2008;118:629–639. PubMed PMC

Suzuki H, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011;22:1795–1803. doi: 10.1681/ASN.2011050464. PubMed DOI PMC

Suzuki H, et al. Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest. 2009;119:1668–1677. PubMed PMC

Singh R, Bandyopadhyay D. MUC1: a target molecule for cancer therapy. Cancer Biol Ther. 2007;6:481–486. doi: 10.4161/cbt.6.4.4201. PubMed DOI

Lloyd KO, Burchell J, Kudryashov V, Yin BW, Taylor-Papadimitriou J. Comparison of O-linked carbohydrate chains in MUC-1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines. Demonstration of simpler and fewer glycan chains in tumor cells. J Biol Chem. 1996;271:33325–33334. doi: 10.1074/jbc.271.52.33317. PubMed DOI

Julien S, et al. Stable expression of sialyl-Tn antigen in T47-D cells induces a decrease of cell adhesion and an increase of cell migration. Breast Cancer Res Treat. 2005;90:77–84. doi: 10.1007/s10549-004-3137-3. PubMed DOI

Pinho S, et al. Biological significance of cancer-associated sialyl-Tn antigen: modulation of malignant phenotype in gastric carcinoma cells. Cancer Lett. 2007;249:157–170. doi: 10.1016/j.canlet.2006.08.010. PubMed DOI

Wandall HH, et al. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. Cancer Res. 2010;70:1306–1313. doi: 10.1158/0008-5472.CAN-09-2893. PubMed DOI PMC

Finn OJ. Cancer immunology. N Engl J Med. 2008;358:2704–2715. doi: 10.1056/NEJMra072739. PubMed DOI

von Mensdorff-Pouilly S, et al. Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours. Eur J Cancer. 1996;32A:1325–1331. doi: 10.1016/0959-8049(96)00048-2. PubMed DOI

Blixt O, et al. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis. Breast Cancer Res. 2011;13:R25. doi: 10.1186/bcr2841. PubMed DOI PMC

Takahashi K, et al. Naturally occurring structural isomers in serum IgA1 O-glycosylation. J Proteome Res. 2012;11:692–702. doi: 10.1021/pr200608q. PubMed DOI PMC

Takahashi K, et al. Clustered O-glycans of IgA1: defining macro- and microheterogeneity by use of electron capture/transfer dissociation. Mol Cell Proteomics. 2010;9:2545–2557. doi: 10.1074/mcp.M110.001834. PubMed DOI PMC

Novak J, Mestecky J (2009) IgA Immune-complex. In: Lai KN (ed) Recent advances in IgA nephropathy, Imperial College Press and the World Scientific Publisher, Hong Kong, p 177–191

Mattu TS, et al. The glycosylation and structure of human serum IgA1, Fab, and Fc regions and the role of N-glycosylation on Fcα receptor interactions. J Biol Chem. 1998;273:2260–2272. doi: 10.1074/jbc.273.4.2260. PubMed DOI

Sihlbom C, et al. Localization of O-glycans in MUC1 glycoproteins using electron-capture dissociation fragmentation mass spectrometry. Glycobiology. 2009;19:375–381. doi: 10.1093/glycob/cwn144. PubMed DOI

Muller S, Hanisch FG. Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. High density and prevalent core 2-based glycosylation. J Biol Chem. 2002;277:26103–26112. doi: 10.1074/jbc.M202921200. PubMed DOI

Tarp MA, Clausen H. Mucin-type O-glycosylation and its potential use in drug and vaccine development. Biochim Biophys Acta. 2008;1780:546–563. doi: 10.1016/j.bbagen.2007.09.010. PubMed DOI

Backstrom M, et al. Recombinant MUC1 mucin with a breast cancer-like O-glycosylation produced in large amounts in Chinese-hamster ovary cells. Biochem J. 2003;376:677–686. doi: 10.1042/BJ20031130. PubMed DOI PMC

Mall AS. Analysis of mucins: role in laboratory diagnosis. J Clin Pathol. 2008;61:1018–1024. doi: 10.1136/jcp.2008.058057. PubMed DOI

Storr SJ, et al. The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient’s serum. Glycobiology. 2008;18:456–462. doi: 10.1093/glycob/cwn022. PubMed DOI

Napoletano C, et al. Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells. Cancer Res. 2007;67:8358–8367. doi: 10.1158/0008-5472.CAN-07-1035. PubMed DOI

Wahrenbrock MG, Varki A. Multiple hepatic receptors cooperate to eliminate secretory mucins aberrantly entering the bloodstream: are circulating cancer mucins the “tip of the iceberg”? Cancer Res. 2006;66:2433–2441. doi: 10.1158/0008-5472.CAN-05-3851. PubMed DOI

Bennett EP, et al. Control of mucin-type O-glycosylation—a classification of the polypeptide GalNAc-transferase gene family. Glycobiology. 2012;22:736–756. PubMed PMC

Gerken TA, et al. Emerging paradigms for the initiation of mucin-type protein O-glycosylation by the polypeptide GalNAc transferase family of glycosyltransferases. J Biol Chem. 2011;286:14493–14507. doi: 10.1074/jbc.M111.218701. PubMed DOI PMC

Rottger S, et al. Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus. J Cell Sci. 1998;111(Pt 1):45–60. PubMed

Gill DJ, Chia J, Senewiratne J, Bard F. Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes. J Cell Biol. 2010;189:843–858. doi: 10.1083/jcb.201003055. PubMed DOI PMC

Iwasaki H, et al. Initiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2. J Biol Chem. 2003;278:5613–5621. doi: 10.1074/jbc.M211097200. PubMed DOI

Wandall HH, et al. The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate-binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation. Glycobiology. 2007;17:374–387. doi: 10.1093/glycob/cwl082. PubMed DOI

Raska M, et al. Role of GalNAc-transferases in the synthesis of aberrant IgA1 O-glycans in IgA nephropathy. J Am Soc Nephrol. 2011;22:625A.

Bennett EP, et al. Cloning and characterization of a close homologue of human UDP-N-acetyl-alpha-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy. J Biol Chem. 1999;274:25362–25370. doi: 10.1074/jbc.274.36.25362. PubMed DOI

Wandall HH, et al. Substrate specificities of three members of the human UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3. J Biol Chem. 1997;272:23503–23514. doi: 10.1074/jbc.272.38.23503. PubMed DOI

Schwientek T, et al. Functional conservation of subfamilies of putative UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases in Drosophila, Caenorhabditis elegans, and mammals. One subfamily composed of l(2)35Aa is essential in Drosophila . J Biol Chem. 2002;277:22623–22638. doi: 10.1074/jbc.M202684200. PubMed DOI

Cheng L, et al. Characterization of a novel human UDP-GalNAc transferase, pp-GalNAc-T15. FEBS Lett. 2004;566:17–24. doi: 10.1016/j.febslet.2004.03.108. PubMed DOI

Zhang Y, et al. Cloning and characterization of a new human UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase, designated pp-GalNAc-T13, that is specifically expressed in neurons and synthesizes GalNAc α-serine/threonine antigen. J Biol Chem. 2003;278:573–584. doi: 10.1074/jbc.M203094200. PubMed DOI

Wang H, et al. Cloning and characterization of a novel UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, pp-GalNAc-T14. Biochem Biophys Res Commun. 2003;300:738–744. doi: 10.1016/S0006-291X(02)02908-X. PubMed DOI

Hassan H, et al. The lectin domain of UDP-N-acetyl-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase-T4 directs its glycopeptide specificities. J Biol Chem. 2000;275:38197–38205. doi: 10.1074/jbc.M005783200. PubMed DOI

Brooks SA, Carter TM, Bennett EP, Clausen H, Mandel U. Immunolocalisation of members of the polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T) family is consistent with biologically relevant altered cell surface glycosylation in breast cancer. Acta Histochem. 2007;109:273–284. doi: 10.1016/j.acthis.2007.02.009. PubMed DOI

Mandel U, et al. Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas: immunohistological evaluation using monoclonal antibodies to three members of the GalNAc-transferase family. Glycobiology. 1999;9:43–52. doi: 10.1093/glycob/9.1.43. PubMed DOI

Marcos NT, et al. Polypeptide GalNAc-transferases, ST6GalNAc-transferase I, and ST3Gal-transferase I expression in gastric carcinoma cell lines. J Histochem Cytochem. 2003;51:761–771. doi: 10.1177/002215540305100607. PubMed DOI

Cooper LS, et al. Expression of GalNAc transferases in breast tissues and cell lines. J Pathol. 1999;187:26A–26A.

Berois N, et al. UDP-N-acetyl-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 as a new immunohistochemical breast cancer marker. J Histochem Cytochem. 2006;54:317–328. doi: 10.1369/jhc.5A6783.2005. PubMed DOI

Freire T, et al. UDP-N-acetyl-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase 6 (ppGalNAc-T6) mRNA as a potential new marker for detection of bone marrow-disseminated breast cancer cells. Int J Cancer. 2006;119:1383–1388. doi: 10.1002/ijc.21959. PubMed DOI

Park JH, et al. Critical roles of mucin 1 glycosylation by transactivated polypeptide N-acetylgalactosaminyltransferase 6 in mammary carcinogenesis. Cancer Res. 2010;70:2759–2769. doi: 10.1158/0008-5472.CAN-09-3911. PubMed DOI

Wu C, et al. N-Acetylgalactosaminyltransferase-14 as a potential biomarker for breast cancer by immunohistochemistry. BMC Cancer. 2010;10:123. doi: 10.1186/1471-2407-10-123. PubMed DOI PMC

Wagner KW, et al. Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med. 2007;13:1070–1077. doi: 10.1038/nm1627. PubMed DOI

Gray-McGuire C, et al. Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22. Cancer Res. 2010;70:5409–5418. doi: 10.1158/0008-5472.CAN-10-0188. PubMed DOI PMC

Guda K, et al. Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. Proc Natl Acad Sci USA. 2009;106:12921–12925. doi: 10.1073/pnas.0901454106. PubMed DOI PMC

Wada Y, et al. Comparison of methods for profiling O-glycosylation: Human Proteome Organisation Human Disease Glycomics/Proteome Initiative multi-institutional study of IgA1. Mol Cell Proteomics. 2010;9:719–727. doi: 10.1074/mcp.M900450-MCP200. PubMed DOI PMC

Ju T, Brewer K, D’Souza A, Cummings RD, Canfield WM. Cloning and expression of human core 1 β1,3-galactosyltransferase. J Biol Chem. 2002;277:178–186. doi: 10.1074/jbc.M109060200. PubMed DOI

Wang Y, et al. Cosmc is an essential chaperone for correct protein O-glycosylation. Proc Natl Acad Sci USA. 2010;107:9228–9233. doi: 10.1073/pnas.0914004107. PubMed DOI PMC

Ju T, Cummings RD. A unique molecular chaperone Cosmc required for activity of the mammalian core 1 β 3-galactosyltransferase. Proc Natl Acad Sci USA. 2002;99:16613–16618. doi: 10.1073/pnas.262438199. PubMed DOI PMC

Charlier E, et al. SHIP-1 inhibits CD95/APO-1/Fas-induced apoptosis in primary T lymphocytes and T leukemic cells by promoting CD95 glycosylation independently of its phosphatase activity. Leukemia. 2010;24:821–832. doi: 10.1038/leu.2010.9. PubMed DOI

Dall’Olio F, Chiricolo M. Sialyltransferases in cancer. Glycoconj J. 2001;18:841–850. doi: 10.1023/A:1022288022969. PubMed DOI

Harduin-Lepers A, et al. The human sialyltransferase family. Biochimie. 2001;83:727–737. doi: 10.1016/S0300-9084(01)01301-3. PubMed DOI

Gharavi AG, et al. Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy. J Am Soc Nephrol. 2008;19:1008–1014. doi: 10.1681/ASN.2007091052. PubMed DOI PMC

Raska M, et al. Identification and characterization of CMP-NeuAc:GalNAc-IgA1 α2,6-sialyltransferase in IgA1-producing cells. J Mol Biol. 2007;369:69–78. doi: 10.1016/j.jmb.2007.03.002. PubMed DOI PMC

Marcos NT, et al. Role of the human ST6GalNAc-I and ST6GalNAc-II in the synthesis of the cancer-associated sialyl-Tn antigen. Cancer Res. 2004;64:7050–7057. doi: 10.1158/0008-5472.CAN-04-1921. PubMed DOI

Suzuki H, et al. Mechanisms of aberrant glycosylation of IgA1 in patients with IgA nephropathy. J Am Soc Nephrol. 2009;20:301A.

Dalziel M, et al. The relative activities of the C2GnT1 and ST3Gal-I glycosyltransferases determine O-glycan structure and expression of a tumor-associated epitope on MUC1. J Biol Chem. 2001;276:11007–11015. doi: 10.1074/jbc.M006523200. PubMed DOI

Brockhausen I, Yang JM, Burchell J, Whitehouse C, Taylor-Papadimitriou J. Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer cells. Eur J Biochem. 1995;233:607–617. doi: 10.1111/j.1432-1033.1995.607_2.x. PubMed DOI

Hanisch FG, Stadie TR, Deutzmann F, Peter-Katalinic J. MUC1 glycoforms in breast cancer—cell line T47D as a model for carcinoma-associated alterations of O-glycosylation. Eur J Biochem. 1996;236:318–327. doi: 10.1111/j.1432-1033.1996.00318.x. PubMed DOI

Sewell R, et al. The ST6GalNAc-I sialyltransferase localizes throughout the Golgi and is responsible for the synthesis of the tumor-associated sialyl-Tn O-glycan in human breast cancer. J Biol Chem. 2006;281:3586–3594. doi: 10.1074/jbc.M511826200. PubMed DOI

Ju T, et al. Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc. Cancer Res. 2008;68:1636–1646. doi: 10.1158/0008-5472.CAN-07-2345. PubMed DOI

Litvinov SV, Hilkens J. The epithelial sialomucin, episialin, is sialylated during recycling. J Biol Chem. 1993;268:21364–21371. PubMed

Avrameas S, Ternynck T (1998) Natural antibodies. In: Delves PJ, Roitt IM (eds) Encyclopedia of immunology. Academic Press, San Diego, p 1806–1809

Brandlein S, et al. Cysteine-rich fibroblast growth factor receptor 1, a new marker for precancerous epithelial lesions defined by the human monoclonal antibody PAM-1. Cancer Res. 2003;63:2052–2061. PubMed

Coutinho A, Kazatchkine MD, Avrameas S. Natural autoantibodies. Curr Opin Immunol. 1995;7:812–818. doi: 10.1016/0952-7915(95)80053-0. PubMed DOI

Avrameas S, Ternynck T, Tsonis IA, Lymberi P. Naturally occurring B-cell autoreactivity: a critical overview. J Autoimmun. 2007;29:213–218. doi: 10.1016/j.jaut.2007.07.010. PubMed DOI

Vollmers HP, Brandlein S. Natural antibodies and cancer. J Autoimmun. 2007;29:295–302. doi: 10.1016/j.jaut.2007.07.013. PubMed DOI

Brandlein S, et al. Natural IgM antibodies and immunosurveillance mechanisms against epithelial cancer cells in humans. Cancer Res. 2003;63:7995–8005. PubMed

Mouthon L, et al. Analysis of the normal human IgG antibody repertoire. Evidence that IgG autoantibodies of healthy adults recognize a limited and conserved set of protein antigens in homologous tissues. J Immunol. 1995;154:5769–5778. PubMed

Springer GF. Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. J Mol Med. 1997;75:594–602. doi: 10.1007/s001090050144. PubMed DOI

Bray J, MacLean GD, Dusel FJ, McPherson TA. Decreased levels of circulating lytic anti-T in the serum of patients with metastatic gastrointestinal cancer: a correlation with disease burden. Clin Exp Immunol. 1982;47:176–182. PubMed PMC

Macher BA, Galili U. The Galα1,3Galβ1,4GlcNAc-R (α-Gal) epitope: a carbohydrate of unique evolution and clinical relevance. Biochim Biophys Acta. 2008;1780:75–88. doi: 10.1016/j.bbagen.2007.11.003. PubMed DOI PMC

Galili U, Mandrell RE, Hamadeh RM, Shohet SB, Griffiss JM. Interaction between human natural anti-α-galactosyl immunoglobulin G and bacteria of the human flora. Infect Immun. 1988;56:1730–1737. PubMed PMC

Baumgarth N, Tung JW, Herzenberg LA. Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion. Springer Semin Immunopathol. 2005;26:347–362. doi: 10.1007/s00281-004-0182-2. PubMed DOI

Gharavi AG, et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet. 2011;43:321–327. doi: 10.1038/ng.787. PubMed DOI PMC

O’Boyle KP, et al. Immunization of colorectal cancer patients with modified ovine submaxillary gland mucin and adjuvants induces IgM and IgG antibodies to sialylated Tn. Cancer Res. 1992;52:5663–5667. PubMed

MacLean GD, et al. Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant. Cancer Immunol Immunother. 1993;36:215–222. doi: 10.1007/BF01740902. PubMed DOI PMC

Longenecker BM, Reddish M, Koganty R, MacLean GD. Immune responses of mice and human breast cancer patients following immunization with synthetic sialyl-Tn conjugated to KLH plus detox adjuvant. Ann N Y Acad Sci. 1993;690:276–291. doi: 10.1111/j.1749-6632.1993.tb44016.x. PubMed DOI

Longenecker BM, Reddish M, Koganty R, MacLean GD. Specificity of the IgG response in mice and human breast cancer patients following immunization against synthetic sialyl-Tn, an epitope with possible functional significance in metastasis. Adv Exp Med Biol. 1994;353:105–124. doi: 10.1007/978-1-4615-2443-4_11. PubMed DOI

MacLean GD, Miles DW, Rubens RD, Reddish MA, Longenecker BM. Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide. J Immunother Emphasis Tumor Immunol. 1996;19:309–316. doi: 10.1097/00002371-199607000-00006. PubMed DOI

Guo Z, Wang Q. Recent development in carbohydrate-based cancer vaccines. Curr Opin Chem Biol. 2009;13:608–617. doi: 10.1016/j.cbpa.2009.08.010. PubMed DOI PMC

Gilewski TA, et al. Immunization of high-risk breast cancer patients with clustered STn-KLH conjugate plus the immunologic adjuvant QS-21. Clin Cancer Res. 2007;13:2977–2985. doi: 10.1158/1078-0432.CCR-06-2189. PubMed DOI

Slovin SF, et al. Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: clinical trial results with α-N-acetylgalactosamine-O-serine/threonine conjugate vaccine. J Clin Oncol. 2003;21:4292–4298. doi: 10.1200/JCO.2003.04.112. PubMed DOI

Slovin SF, et al. A bivalent conjugate vaccine in the treatment of biochemically relapsed prostate cancer: a study of glycosylated MUC-2-KLH and Globo H-KLH conjugate vaccines given with the new semi-synthetic saponin immunological adjuvant GPI-0100 OR QS-21. Vaccine. 2005;23:3114–3122. doi: 10.1016/j.vaccine.2005.01.072. PubMed DOI

Elkon K, Casali P. Nature and functions of autoantibodies. Nat Clin Pract Rheumatol. 2008;4:491–498. doi: 10.1038/ncprheum0895. PubMed DOI PMC

Ni J, Song H, Wang Y, Stamatos NM, Wang LX. Toward a carbohydrate-based HIV-1 vaccine: synthesis and immunological studies of oligomannose-containing glycoconjugates. Bioconjug Chem. 2006;17:493–500. doi: 10.1021/bc0502816. PubMed DOI

Dziadek S, Hobel A, Schmitt E, Kunz H. A fully synthetic vaccine consisting of a tumor-associated glycopeptide antigen and a T-cell epitope for the induction of a highly specific humoral immune response. Angew Chem Int Ed Engl. 2005;44:7630–7635. doi: 10.1002/anie.200501594. PubMed DOI

Cremer GA, et al. Synthesis and biological evaluation of a multiantigenic Tn/TF-containing glycopeptide mimic of the tumor-related MUC1 glycoprotein. ChemMedChem. 2006;1:965–968. doi: 10.1002/cmdc.200600104. PubMed DOI

Lo-Man R, et al. A fully synthetic therapeutic vaccine candidate targeting carcinoma-associated Tn carbohydrate antigen induces tumor-specific antibodies in nonhuman primates. Cancer Res. 2004;64:4987–4994. doi: 10.1158/0008-5472.CAN-04-0252. PubMed DOI

Ingale S, Wolfert MA, Gaekwad J, Buskas T, Boons GJ. Robust immune responses elicited by a fully synthetic three-component vaccine. Nat Chem Biol. 2007;3:663–667. doi: 10.1038/nchembio.2007.25. PubMed DOI PMC

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