Relative stabilities of IgG1 and IgG4 Fab domains: Influence of the light-heavy interchain disulfide bond architecture

Protein Science

Volumn 21, Issue 9, 2012, Pages 1315-1322

  Heads, James T ^a   Adams, Ralph ^a   D'Hooghe, Lena E ^a   Page, Matt J T ^a   Humphreys, David P ^a   Popplewell, Andrew G ^a   Lawson, Alastair D ^a   Henry, Alistair J ^a  

^a UCB PHARMA   (Belgium)

Author keywords

Disulfide bond; Heavy chain; IgG1; IgG4; Light chain; Thermal stability; Thermofluor

Indexed keywords

ACETIC ACID; IMMUNOGLOBULIN F(AB) FRAGMENT; IMMUNOGLOBULIN FC FRAGMENT; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G1 ANTIBODY; IMMUNOGLOBULIN G4; SODIUM CHLORIDE;

ARTICLE; CH1 CONSTANT DOMAIN; DISULFIDE BOND; LIGHT HEAVY INTERCHAIN DISULFIDE BOND; PRIORITY JOURNAL; PROTEIN DOMAIN; THERMOSTABILITY;

AMINO ACID SEQUENCE; ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; CHO CELLS; CRICETINAE; DISULFIDES; HEK293 CELLS; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; IMMUNOGLOBULIN G; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN LIGHT CHAINS; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; MUTATION; PROTEIN STABILITY; PROTEIN STRUCTURE, TERTIARY; TEMPERATURE;

EID: 84865435437     PISSN: 09618368     EISSN: 1469896X     Source Type: Journal    
DOI: 10.1002/pro.2118     Document Type: Article

References (37)

1. Wu TT, Kabat EA (1970) An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med 132:211-250.
2. Chothia C, Lesk AM (1987) Canonical structures for the hypervariable regions of immunoglobulins. J Mol Biol 196:901-917. (Pubitemid 17127946)
3. Burton D, Gregory L, Jefferies R (1986) Aspects of the molecular structure of IgG subclasses. Monogra Allerg 19:7-35.
4. Correia IR (2010) Stability of IgG isotypes in serum. mAbs 2:221-232.
5. Wypych J, Li M, Guo A, Zhang Z, Martinez T, Allen MJ, Fodor S, Kelner DN, Flynn GC, Liu YD, Bondarenko PV, Ricci MS, Dillon TM, Balland A (2008) Human IgG2 antibodies display disulfide-mediated structural isoforms. J Biol Chem 283:16194-16205.
6. Saphire EO, Stanfield RL, Crispin MDM, Parren PWHI, Rudd PM, Dwek RA, Burton DR, Wilson IA (2002) Contrasting IgG structures reveal extreme asymmetry and flexibility. J Mol Biol 319:9-18. (Pubitemid 34729482)
7. Saphire EO, Parren PW, Pantophlet R, Zwick MB, Morris GM, Rudd PM, Dwek RA, Stanfield RL, Burton DR, Wilson IA (2001) Crystal structure of a neutralizing human IgG against HIV-1: a template for vaccine design. Science 293:1155-11599.
8. Sibéril S, Dutertrea CA, Fridman WH, Teillaud JH (2007) FcγR: the key to optimize therapeutic antibodies? Crit Rev Oncol Hematol 62:26-33. (Pubitemid 46343788)
9. Salfeld JG (2007) Isotype selection in antibody engineering. Nat Biotechnol 25:1369-1372.
10. Van Dijk MA, Van de Winkel JG (2001) Human antibodies as next generation therapeutics. Curr Opin Chem Biol 5:368-374. (Pubitemid 32900507)
11. Carter PJ (2006) Potent antibody therapeutics by design. Nat Rev Immunol 6:343-357.
12. Jiang XR, Song A, Bergelson S, Arroll T, Parekh B, May K, Chung S, Strouse R, Mire-Sluis A, Schenerman M (2011) Advances in the assessment and control of the effector functions of therapeutic antibodies. Nat Rev Drug Discov 10:101-111.
13. Yoo EM, Wims LA, Chan LA, Morrison SL (2003) Human IgG2 can form covalent dimers. Immunology 170:3134-3138. (Pubitemid 36302189)
14. Liu YD, Chen X, Enk JZ-van, Plant M, Dillon TM, Flynn GC (2008) Human IgG2 antibody disulfide rearrangement in vivo. J Biol Chem 283:29266-29272.
15. Dillon TM, Ricci MS, Vezina C, Flynn GC, Liu YD, Rehder DS, Plant M, Henkle B, Li Y, Deechongkit S, Varnum B, Wypych J, Balland A, Bondarenko PV (2008) Structural and functional characterization of disulfide isoforms of the human IgG2 subclass. J Biol Chem 283:16206-16215.
16. Aalberse RC, Schuurman J (2002) IgG4 breaking the rules. Immunology 105:9-19. (Pubitemid 34128035)
17. Schuurman J, Perdok GJ, Gorter AD, Aalberse RC (2001) The inter-heavy chain disulfide bonds of IgG4 are in equilibrium with intra-chain disulfide bonds. Mol Immunol 38:1-8. (Pubitemid 32718637)
18. van der Neut Kolfschoten M, Schuurman, J, Losen, M, Bleeker WK, Martínez-Martínez P, Vermeulen E, den Bleker TH, Wiegman L, Vink T, Aarden LA, De Baets MH, van de Winkel JGJ, Aalberse RC, Parren PWHI (2007) Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 317: 1554-1557. (Pubitemid 47417435)
19. Bloom JW, Madanat MS, Marriott D, Wong T, Chan SY (1997) Intrachain disulfide bond in the core hinge region of human IgG4. Protein Sci 6:407-415. (Pubitemid 27079933)
20. Angal S, King DJ, Bodmer MW, Turner A, Lawson AD, Roberts G, Pedley B, Adair JR (1993) A single amino acid substitution abolishes the heterogeneity of chimeric mouse/human (IgG4) antibody. Mol Immunol 30:105-108. (Pubitemid 223036868)
21. Ewert S, Honegger A, Plückthun A (2004) Stability improvement of antibodies for extracellular and intracellular applications: CDR grafting to stable frameworks and structure-based framework engineering. Methods 34:184-199. (Pubitemid 39092813)
22. Caravella, JA, Wang D, Glaser SM, Lugovskoy A (2010) Structure-guided design of antibodies. Curr Comput-Aided Drug Des 6:128-138.
23. Demarest SJ, Chen G, Kimmel BE, Gustafson D, Wu J, Salbato J, Poland J, Elia M, Tan X, Wong K, Short J, Hansen G (2006) Engineering stability into Escherichia coli secreted Fabs leads to increased functional expression. Protein Eng Des Sel 19:325-336. (Pubitemid 43999643)
24. Monsellier E, Bedouelle H (2006) Improving the stability of an antibody variable fragment by a combination of knowledge-based approaches: validation and mechanisms. J Mol Biol 362:580-593 (Pubitemid 44307161)
25. Martineau P, Betton JM (1999) In vitro folding and thermodynamic stability of an antibody fragmentselected in vivo for high expression levels in Escherichia coli cytoplasm. J Mol Biol 292:921-299.
26. Ionescu RM, Vlasak J, Price C, Kirchmeier M (2008) Contribution of variable domains to the stability of humanized IgG1 monoclonal antibodies. J Pharmacol Sci 97:1414-1426.
27. Willuda J, Honegger A, Waibel R, Schubiger PA, Stahel R, Zangemeister-Wittke U, Plückthun A (1999) High thermal stability is essential for tumor targeting of antibody fragments: engineering of a humanized anti-epithelial glycoprotein-2 (epithelial cell adhesion molecule) single-chain Fv fragment. Cancer Res 59:5758-57567.
28. Chennamsetty N, Voynov V, Kayser V, Helk B, Trout BL (2009) Design of therapeutic proteins with enhanced stability. Proc Natl Acad Sci USA 106: 11937-11942.
29. Peters SJ, Smales MC, Henry AJ, Stephens PE, West S, Humphreys DP (2012) Engineering an improved IgG4 molecule with reduced disulphide bond heterogeneity and increased Fab domain thermal stability. PMID:22610095 [Medline].
30. Röthlisberger D, Honegger A, Plückthun A (2005) Domain interactions in the Fab fragment: a comparative evaluation of the single-chain Fv and Fab format engineered with variable domains of different stability. J Mol Biol 347:773-789.
31. Garber E, Demarest SJ (2007) A broad range of Fab stabilities within a host of therapeutic IgGs. Biochem Biophys Res Commun 355:751-757. (Pubitemid 46343718)
32. Ishikawa T, Ito T, Endo R, Nakagawa K, Sawa E, Wakamatsu K (2010) Influence of pH on heat-induced aggregation and degradation of therapeutic monoclonal antibodies. Biol Pharm Bull 33:1413-1417.
33. Pantoliano MW, Petrella EC, Kwasnoski JD, Lobanov VS, Myslik J, Graf E, Carver T, Asel E, Springer BA, Lane P, Salemme FR (2001) High-density miniaturized thermal shift assays as a general strategy for drug discovery. J Biomol Screening 6:429-440. (Pubitemid 34052847)
34. Cummings MD, Farnum MA, Nelen MI (2006) Universal screening methods and applications of Thermo-Fluor. J Biomol Screening 11:854-863. (Pubitemid 44562327)
35. Ericsson UB, Hallberg BM, Detitta GT, Dekker N, Nordlund P (2006) Thermofluor-based high-throughput stability optimization of proteins for structural studies. Anal Biochem 357:289-298. (Pubitemid 44430091)
36. He F, Hogan S, Latypov RF, Narhi LO, Razinkov VI (2010) High throughput thermostability screening of monoclonal antibody formulations. J Pharm Sci 99:1707-1720.
37. Vermeer AW, Norde W (2000) The thermal stability of immunoglobulin: unfolding and aggregation of a multi-domain protein. Biophys J 78:394-404. (Pubitemid 30207148)