Segmental Flexibility and Complement Fixation of Genetically Engineered Chimeric Human, Rabbit and Mouse Antibodies

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1988 Jul 1

PMID 3138110

Citations 88

Authors

J L Dangl

T G Wensel

S L Morrison

L Stryer

L A Herzenberg

V T Oi

Affiliations

Soon will be listed here.

Abstract

We generated a family of chimeric immunoglobulin G (IgG) molecules having identical antigen-combining sites for the dansyl (DNS) hapten, in conjunction with nine heavy chain constant (CH) regions. This family of antibody molecules allows comparison of CH dependent properties independent of possible variable region contributions to IgG function. The segmental flexibility and complement fixation activity were measured of six genetically engineered molecules (the four human IgG isotypes, mouse IgG3 and rabbit IgG) and the remaining three mouse IgG isotypes, (IgG1, IgG2a and IgG2b), isolated previously by somatic cell genetic techniques. These properties of antibody molecules each correlate with the length of the immunoglobulin hinge region which separate the first and second CH (CH1 and CH2) domains. These results attribute a structural basis for two critical properties of antibody molecules.

Citing Articles

Type 5 secretion system antigens as vaccines against Gram-negative bacterial infections.

Da Costa R, Rooke J, Wells T, Cunningham A, Henderson I NPJ Vaccines. 2024; 9(1):159.

PMID: 39218947 PMC: 11366766. DOI: 10.1038/s41541-024-00953-6.

Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement system.

Ilinykh P, Huang K, Gunn B, Kuzmina N, Kedarinath K, Jurado-Cobena E Commun Biol. 2024; 7(1):871.

PMID: 39020082 PMC: 11255267. DOI: 10.1038/s42003-024-06556-0.

Emerging role of complement in COVID-19 and other respiratory virus diseases.

Xiao M, Ellsworth C, Qin X Cell Mol Life Sci. 2024; 81(1):94.

PMID: 38368584 PMC: 10874912. DOI: 10.1007/s00018-024-05157-8.

Complement is activated by elevated IgG3 hexameric platforms and deposits C4b onto distinct antibody domains.

Abendstein L, Dijkstra D, Tjokrodirijo R, Van Veelen P, Trouw L, Hensbergen P Nat Commun. 2023; 14(1):4027.

PMID: 37419978 PMC: 10328927. DOI: 10.1038/s41467-023-39788-5.

Modulating antibody effector functions by Fc glycoengineering.

Garcia-Alija M, Van Moer B, Sastre D, Azzam T, Du J, Trastoy B Biotechnol Adv. 2023; 67:108201.

PMID: 37336296 PMC: 11027751. DOI: 10.1016/j.biotechadv.2023.108201.

References

Valentine R, Green N . Electron microscopy of an antibody-hapten complex. J Mol Biol. 1967; 27(3):615-7. DOI: 10.1016/0022-2836(67)90063-0. View

Feinstein A, ROWE A . MOLECULAR MECHANISM OF FORMATION OF AN ANTIGEN-ANTIBODY COMPLEX. Nature. 1965; 205:147-9. DOI: 10.1038/205147a0. View

Isenman D, DORRINGTON K, Painter R . The structure and function of immunoglobulin domains. II. The importance of interchain disulfide bonds and the possible role of molecular flexibility in the interaction between immunoglobulin G and complement. J Immunol. 1975; 114(6):1726-9. View

Beale D, Feinstein A . Structure and function of the constant regions of immunoglobulins. Q Rev Biophys. 1976; 9(2):135-80. DOI: 10.1017/s0033583500002390. View

Huber R, Deisenhofer J, Colman P, Matsushima M, PALM W . Crystallographic structure studies of an IgG molecule and an Fc fragment. Nature. 1976; 264(5585):415-20. DOI: 10.1038/264415a0. View

Silverton E, Navia M, Davies D . Three-dimensional structure of an intact human immunoglobulin. Proc Natl Acad Sci U S A. 1977; 74(11):5140-4. PMC: 432116. DOI: 10.1073/pnas.74.11.5140. View

Hickman S, Kornfeld S . Effect of tunicamycin on IgM, IgA, and IgG secretion by mouse plasmacytoma cells. J Immunol. 1978; 121(3):990-6. View

DORRINGTON K . The structural basis for the functional versatility of immunoglobulin G1. Can J Biochem. 1978; 56(12):1087-101. DOI: 10.1139/o78-172. View

Parks D, Bryan V, Oi V, Herzenberg L . Antigen-specific identification and cloning of hybridomas with a fluorescence-activated cell sorter. Proc Natl Acad Sci U S A. 1979; 76(4):1962-6. PMC: 383513. DOI: 10.1073/pnas.76.4.1962. View

10.

Amzel L, POLJAK R . Three-dimensional structure of immunoglobulins. Annu Rev Biochem. 1979; 48:961-97. DOI: 10.1146/annurev.bi.48.070179.004525. View

11.

Honjo T, Obata M, Kataoka T, Kawakami T, Takahashi N, Mano Y . Cloning and complete nucleotide sequence of mouse immunoglobulin gamma 1 chain gene. Cell. 1979; 18(2):559-68. DOI: 10.1016/0092-8674(79)90072-2. View

12.

Kataoka T, Takahashi N, Obata M, Honjo T . Complete nucleotide sequence of immunoglobulin gamma2b chain gene cloned from newborn nouse DNA. Nature. 1980; 283(5749):786-9. DOI: 10.1038/283786a0. View

13.

Marquart M, Deisenhofer J, Huber R, PALM W . Crystallographic refinement and atomic models of the intact immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 A and 1.0 A resolution. J Mol Biol. 1980; 141(4):369-91. DOI: 10.1016/0022-2836(80)90252-1. View

14.

Sikorav J, Auffray C, Rougeon F . Structure of the constant and 3' untranslated regions of the murine Balb/c gamma 2a heavy chain messenger RNA. Nucleic Acids Res. 1980; 8(14):3143-55. PMC: 324361. DOI: 10.1093/nar/8.14.3143. View

15.

Klein M, Haeffner-Cavaillon N, Isenman D, Rivat C, Navia M, Davies D . Expression of biological effector functions by immunoglobulin G molecules lacking the hinge region. Proc Natl Acad Sci U S A. 1981; 78(1):524-8. PMC: 319086. DOI: 10.1073/pnas.78.1.524. View

16.

Hanson D, Yguerabide J, Schumaker V . Segmental flexibility of immunoglobulin G antibody molecules in solution: a new interpretation. Biochemistry. 1981; 20(24):6842-52. DOI: 10.1021/bi00527a016. View

17.

Neuberger M, Rajewsky K . Activation of mouse complement by monoclonal mouse antibodies. Eur J Immunol. 1981; 11(12):1012-6. DOI: 10.1002/eji.1830111212. View

18.

Dangl J, Parks D, Oi V, Herzenberg L . Rapid isolation of cloned isotype switch variants using fluorescence activated cell sorting. Cytometry. 1982; 2(6):395-401. DOI: 10.1002/cyto.990020607. View

19.

Ellison J, Hood L . Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes. Proc Natl Acad Sci U S A. 1982; 79(6):1984-8. PMC: 346106. DOI: 10.1073/pnas.79.6.1984. View

20.

Ellison J, Berson B, HOOD L . The nucleotide sequence of a human immunoglobulin C gamma1 gene. Nucleic Acids Res. 1982; 10(13):4071-9. PMC: 320779. DOI: 10.1093/nar/10.13.4071. View