Mutation of Y407 in the CH3 domain dramatically alters glycosylation and structure of human IgG

mAbs

Volumn 5, Issue 2, 2013, Pages 219-228

  Rose, Rebecca J ^a,b   Van Berkel, Patrick H C ^c   Van Den Bremer, Ewald T J ^c   Labrijn, Aran F ^c   Vink, Tom ^c   Schuurman, Janine ^c   Heck, Albert J R ^a,b   Parren, Paul W H I ^c  

^a UTRECHT UNIVERSITY   (Netherlands)

^b NETHERLANDS PROTEOMICS CENTRE   (Netherlands)

^c GENMAB   (Netherlands)

Author keywords

Antibody structure; Hydrogen deuterium exchange; N linked glycosylation; Native mass spectrometry; Sialic acid

Indexed keywords

GLYCAN; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G4;

ALLOSTERISM; ANTIBODY STRUCTURE; ARTICLE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DEUTERIUM HYDROGEN EXCHANGE; DIMERIZATION; GALACTOSYLATION; GLYCOSYLATION; MASS SPECTROMETRY; MUTATION; SIALYLATION;

ANTIBODY STRUCTURE; HYDROGEN-DEUTERIUM EXCHANGE; N-LINKED GLYCOSYLATION; NATIVE MASS SPECTROMETRY; SIALIC ACID;

ANTIBODIES, MONOCLONAL; DEUTERIUM EXCHANGE MEASUREMENT; GLYCOSYLATION; HUMANS; IMMUNOGLOBULIN G; MASS SPECTROMETRY; MODELS, MOLECULAR; MUTATION; N-ACETYLNEURAMINIC ACID; PROTEIN CONFORMATION; PROTEIN ENGINEERING; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84876584375     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/mabs.23532     Document Type: Article

References (36)

1. Arnold JN, Wormald MR, Sim RB, Rudd PM, Dwek RA. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 2007; 25: 21-50; PMID:17029568; http://dx.doi.org/10.1146/ annurev. immunol.25.022106.141702
2. Elbein AD. The role of N-linked oligosaccharides in glycoprotein function. Trends Biotechnol 1991; 9: 346-52; PMID:1367760; http://dx.doi.org/10. 1016/0167- 7799(91)90117-Z
3. Reichert JM. Marketed therapeutic antibodies compendium. MAbs 2012; 4: 413-5; PMID:22531442; http://dx.doi.org/10.4161/mabs.19931
4. Tsuchiya N, Endo T, Matsuta K, Yoshinoya S, Aikawa T, Kosuge E, et al. Effects of galactose depletion from oligosaccharide chains on immunological activities of human IgG. J Rheumatol 1989; 16: 285-90; PMID:2498512
5. Wright A, Morrison SL. Effect of C2-associated carbohydrate structure on Ig effector function: studies with chimeric mouse-human IgG1 antibodies in glycosylation mutants of Chinese hamster ovary cells. J Immunol 1998; 160: 3393-402; PMID:9531299
6. Hodoniczky J, Zheng YZ, James DC. Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro. Biotechnol Prog 2005; 21: 1644-52; PMID:16321047; http://dx.doi.org/10.1021/bp050228w
7. Shields RL, Lai J, Keck R, O'Connell LY, Hong K, Meng YG, et al. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity. J Biol Chem 2002; 277: 26733-40; PMID:11986321; http://dx.doi.org/10.1074/jbc.M202069200
8. Shinkawa T, Nakamura K, Yamane N, Shoji-Hosaka E, Kanda Y, Sakurada M, et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 2003; 278: 3466-73; PMID:12427744; http://dx.doi.org/10.1074/jbc.M210665200
9. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 2008; 320: 373-6; PMID:18420934; http://dx.doi.org/10.1126/science. 1154315
10. Anthony RM, Wermeling F, Karlsson MCI, Ravetch JV. Identification of a receptor required for the antiinflammatory activity of IVIG. Proc Natl Acad Sci U S A 2008; 105: 19571-8; PMID:19036920; http://dx.doi.org/10.1073/pnas. 0810163105
11. Kaneko Y, Nimmerjahn F, Ravetch JV. Antiinflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 2006; 313: 670-3; PMID:16888140; http://dx.doi.org/10.1126/science. 1129594
12. Scallon BJ, Tam SH, McCarthy SG, Cai AN, Raju TS. Higher levels of sialylated Fc glycans in immunoglobulin G molecules can adversely impact functionality. Mol Immunol 2007; 44: 1524-34; PMID:17045339; http://dx.doi.org/10.1016/j.molimm.2006.09.005
13. Moore GL, Chen H, Karki S, Lazar GA. Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs 2010; 2: 181-9; PMID:20150767; http://dx.doi.org/10.4161/ mabs.2.2.11158
14. Rose RJ, Labrijn AF, van den Bremer ETJ, Loverix S, Lasters I, van Berkel PHC, et al. Quantitative analysis of the interaction strength and dynamics of human IgG4 half molecules by native mass spectrometry. Structure 2011; 19: 1274-82; PMID:21893287; http://dx.doi.org/10.1016/j.str.2011.06.016
15. van der Neut Kolfschoten M, Schuurman J, Losen M, Bleeker WK, Martínez-Martínez P, Vermeulen E, et al. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 2007; 317: 1554-7; PMID:17872445; http://dx.doi.org/10.1126/science.1144603
16. Lund J, Takahashi N, Pound JD, Goodall M, Jefferis R. Multiple interactions of IgG with its core oligosaccharide can modulate recognition by complement and human Fc gamma receptor I and influence the synthesis of its oligosaccharide chains. J Immunol 1996; 157: 4963-9; PMID:8943402
17. Deisenhofer J. Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9- and 2.8-A resolution. Biochemistry 1981; 20: 2361-70; PMID:7236608; http://dx.doi.org/10.1021/bi00512a001
18. Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P. Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol 2003; 325: 979-89; PMID:12527303; http://dx.doi.org/10.1016/S0022- 2836(02)01250-0
19. Sondermann P, Huber R, Oosthuizen V, Jacob U. The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature 2000; 406: 267-73; PMID:10917521; http://dx.doi.org/10.1038/35018508
20. Houde D, Arndt J, Domeier W, Berkowitz S, Engen Jr. Characterization of IgG1 conformation and conformational dynamics by hydrogen/deuterium exchange mass spectrometry. Anal Chem 2009; 81:5966; PMID:19606834; http://dx.doi.org/10. 1021/ ac9009287
21. Houde D, Peng Y, Berkowitz SA, Engen Jr. Posttranslational modifications differentially affect IgG1 conformation and receptor binding. Mol Cell Proteomics 2010; 9: 1716-28; PMID:20103567; http://dx.doi.org/10.1074/mcp. M900540-MCP200
22. Burkitt W, Domann P, O'Connor G. Conformational changes in oxidatively stressed monoclonal antibodies studied by hydrogen exchange mass spectrometry. Protein Sci 2010; 19: 826-35; PMID:20162626; http://dx.doi.org/10.1002/pro.362
23. Carter P. Bispecific human IgG by design. J Immunol Methods 2001; 248: 7-15; PMID:11223065; http://dx.doi.org/10.1016/S0022-1759(00)00339-2
24. Ridgway JBB, Presta LG, Carter P. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 1996; 9: 617-21; PMID:8844834; http://dx.doi.org/10.1093/protein/ 9.7.617
25. Rudd PM, Dwek RA. Glycosylation: heterogeneity and the 3D structure of proteins. Crit Rev Biochem Mol Biol 1997; 32: 1-100; PMID:9063619; http://dx.doi.org/10.3109/10409239709085144
26. Jassal R, Jenkins N, Charlwood J, Camilleri P, Jefferis R, Lund J. Sialylation of human IgG-Fc carbohydrate by transfected rat alpha2,6- sialyltransferase. Biochem Biophys Res Commun 2001; 286: 243-9; PMID:11500028; http://dx.doi.org/10.1006/ bbrc.2001.5382
27. Lund J, Takahashi N, Popplewell A, Goodall M, Pound JD, Tyler R, et al. Expression and characterization of truncated forms of humanized L243 IgG1. Architectural features can influence synthesis of its oligosaccharide chains and affect superoxide production triggered through human Fcgamma receptor I. Eur J Biochem 2000; 267: 7246-57; PMID:11106438; http://dx.doi.org/10.1046/j.1432- 1327.2000.01839.x
28. Stadlmann J, Weber A, Pabst M, Anderle H, Kunert R, Ehrlich HJ, et al. A close look at human IgG sialylation and subclass distribution after lectin fractionation. Proteomics 2009; 9: 4143-53; PMID:19688751; http://dx.doi.org/10. 1002/pmic.200800931
29. Barb AW, Borgert AJ, Liu M, Barany G, Live D. Intramolecular glycan-protein interactions in glycoproteins. Methods Enzymol 2010; 478: 365-88; PMID:20816490; http://dx.doi.org/10.1016/S0076- 6879(10)78018-6
30. Raju TS. Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr Opin Immunol 2008; 20: 471-8; PMID:18606225; http://dx.doi.org/10.1016/j.coi.2008.06.007
31. Anthony RM, Ravetch JV. A novel role for the IgG Fc glycan: the anti-inflammatory activity of sialylated IgG Fcs. J Clin Immunol 2010; 30(Suppl 1):S9-14; PMID:20480216; http://dx.doi.org/10.1007/s10875-010-9405-6
32. Jefferis R. Glycosylation of recombinant antibody therapeutics. Biotechnol Prog 2005; 21: 11-6; PMID:15903235; http://dx.doi.org/10.1021/ bp040016j
33. Jefferis R. Glycosylation of human IgG antibodies: relevance to therapeutic applications. Biopharm 2002; 14: 19-26
34. Labrijn AF, Buijsse AO, van den Bremer ETJ, Verwilligen AYW, Bleeker WK, Thorpe SJ, et al. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. Nat Biotechnol 2009; 27: 767-71; PMID:19620983; http://dx.doi.org/10.1038/nbt.1553
35. van Berkel PHC, Gerritsen J, van Voskuilen E, Perdok G, Vink T, van de Winkel JGJ, et al. Rapid production of recombinant human IgG With improved ADCC effector function in a transient expression system. Biotechnol Bioeng 2010; 105: 350-7; PMID:19739094; http://dx.doi.org/10.1002/bit.22535
36. van Berkel PHC, Gerritsen J, Perdok G, Valbjørn J, Vink T, van de Winkel JGJ, et al. N-linked glycosylation is an important parameter for optimal selection of cell lines producing biopharmaceutical human IgG. Biotechnol Prog 2009; 25: 244-51; PMID:19224598; http://dx.doi.org/10.1002/btpr.92