Abstract
Cell lines have been established that secrete a matched set of human chimeric IgM, IgG1, IgG2, IgG3, IgG4, IgE, and IgA2 antibodies that are directed against the hapten 4-hydroxy-3-nitrophenacetyl. These chimeric antibodies secreted from mouse plasmacytoma cells behave exactly like their authentic human counterparts in SDS-PAGE analysis, binding to protein A and in a wide range of serological assays. The antibodies have been compared in their ability to bind human C1q as well as in their efficacy in mediating lysis of human erythrocytes in the presence of human complement. A major conclusion to emerge is that whereas IgG3 bound C1q better than did IgG1, the chimeric IgG1 was much more effective than all the other IgG subclasses in complement-dependent hemolysis. The IgG1 antibody was also the most effective in mediating antibody-dependent cell-mediated cytotoxicity using both human effector and human target cells. These results suggest that IgG1 might be the favoured IgG subclass for therapeutic applications.
Full Text
The Full Text of this article is available as a PDF (822.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boulianne G. L., Hozumi N., Shulman M. J. Production of functional chimaeric mouse/human antibody. Nature. 1984 Dec 13;312(5995):643–646. doi: 10.1038/312643a0. [DOI] [PubMed] [Google Scholar]
- Brüggemann M., Rajewsky K. Regulation of the antibody response against hapten-coupled erythrocytes by monoclonal antihapten antibodies of various isotypes. Cell Immunol. 1982 Aug;71(2):365–373. doi: 10.1016/0008-8749(82)90270-2. [DOI] [PubMed] [Google Scholar]
- Burton D. R. Immunoglobulin G: functional sites. Mol Immunol. 1985 Mar;22(3):161–206. doi: 10.1016/0161-5890(85)90151-8. [DOI] [PubMed] [Google Scholar]
- Farris M. A., Hardie D., de Lange G., Jefferis R. Immunogenic and antigenic epitopes of immunoglobulins. X: Monoclonal antibodies specific for human IgA, the IgA1 and IgA2 subclasses and an nA2m(2) iso-allotypic epitope. Vox Sang. 1985;48(2):116–121. doi: 10.1111/j.1423-0410.1985.tb00155.x. [DOI] [PubMed] [Google Scholar]
- Flanagan J. G., Lefranc M. P., Rabbitts T. H. Mechanisms of divergence and convergence of the human immunoglobulin alpha 1 and alpha 2 constant region gene sequences. Cell. 1984 Mar;36(3):681–688. doi: 10.1016/0092-8674(84)90348-9. [DOI] [PubMed] [Google Scholar]
- Flanagan J. G., Rabbitts T. H. Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes. Nature. 1982 Dec 23;300(5894):709–713. doi: 10.1038/300709a0. [DOI] [PubMed] [Google Scholar]
- Galfrè G., Milstein C. Preparation of monoclonal antibodies: strategies and procedures. Methods Enzymol. 1981;73(Pt B):3–46. doi: 10.1016/0076-6879(81)73054-4. [DOI] [PubMed] [Google Scholar]
- Hale G., Bright S., Chumbley G., Hoang T., Metcalf D., Munro A. J., Waldmann H. Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood. 1983 Oct;62(4):873–882. [PubMed] [Google Scholar]
- Hale G., Clark M., Waldmann H. Therapeutic potential of rat monoclonal antibodies: isotype specificity of antibody-dependent cell-mediated cytotoxicity with human lymphocytes. J Immunol. 1985 May;134(5):3056–3061. [PubMed] [Google Scholar]
- Huck S., Fort P., Crawford D. H., Lefranc M. P., Lefranc G. Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes. Nucleic Acids Res. 1986 Feb 25;14(4):1779–1789. doi: 10.1093/nar/14.4.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaafar M. I., Lowe J. A., Ling N. R., Jefferis R. Immunogenic and antigenic epitopes of immunoglobulins--V. Reactivity of a panel of monoclonal antibodies with sub-fragments of human Fc gamma and abnormal paraproteins having deletions. Mol Immunol. 1983 Jun;20(6):679–686. doi: 10.1016/0161-5890(83)90012-3. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Liu A. Y., Robinson R. R., Hellström K. E., Murray E. D., Jr, Chang C. P., Hellström I. Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells. Proc Natl Acad Sci U S A. 1987 May;84(10):3439–3443. doi: 10.1073/pnas.84.10.3439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowe J., Bird P., Hardie D., Jefferis R., Ling N. R. Monoclonal antibodies (McAbs) to determinants on human gamma chains: properties of antibodies showing subclass restriction or subclass specificity. Immunology. 1982 Oct;47(2):329–336. [PMC free article] [PubMed] [Google Scholar]
- Milstein C. P., Deverson E. V., Rabbitts T. H. The sequence of the human immunoglobulin mu-delta intron reveals possible vestigial switch segments. Nucleic Acids Res. 1984 Aug 24;12(16):6523–6535. doi: 10.1093/nar/12.16.6523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morrison S. L., Johnson M. J., Herzenberg L. A., Oi V. T. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6851–6855. doi: 10.1073/pnas.81.21.6851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neuberger M. S., Rajewsky K. Activation of mouse complement by monoclonal mouse antibodies. Eur J Immunol. 1981 Dec;11(12):1012–1016. doi: 10.1002/eji.1830111212. [DOI] [PubMed] [Google Scholar]
- Neuberger M. S., Williams G. T., Mitchell E. B., Jouhal S. S., Flanagan J. G., Rabbitts T. H. A hapten-specific chimaeric IgE antibody with human physiological effector function. Nature. 1985 Mar 21;314(6008):268–270. doi: 10.1038/314268a0. [DOI] [PubMed] [Google Scholar]
- Oi V. T., Morrison S. L., Herzenberg L. A., Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. doi: 10.1073/pnas.80.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reth M., Imanishi-Kari T., Rajewsky K. Analysis of the repertoire of anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies in C 57 BL/6 mice by cell fusion. II. Characterization of idiotopes by monoclonal anti-idiotope antibodies. Eur J Immunol. 1979 Dec;9(12):1004–1013. doi: 10.1002/eji.1830091216. [DOI] [PubMed] [Google Scholar]
- Sahagan B. G., Dorai H., Saltzgaber-Muller J., Toneguzzo F., Guindon C. A., Lilly S. P., McDonald K. W., Morrissey D. V., Stone B. A., Davis G. L. A genetically engineered murine/human chimeric antibody retains specificity for human tumor-associated antigen. J Immunol. 1986 Aug 1;137(3):1066–1074. [PubMed] [Google Scholar]
- Schumaker V. N., Calcott M. A., Spiegelberg H. L., Müller-Eberhard H. J. Ultracentifuge studies of the binding of IgG of different subclasses to the Clq subunit of the first component of complement. Biochemistry. 1976 Nov 16;15(23):5175–5181. doi: 10.1021/bi00668a035. [DOI] [PubMed] [Google Scholar]
- Spiegelberg H. L. Biological activities of immunoglobulins of different classes and subclasses. Adv Immunol. 1974;19(0):259–294. doi: 10.1016/s0065-2776(08)60254-0. [DOI] [PubMed] [Google Scholar]
- Sun L. K., Curtis P., Rakowicz-Szulczynska E., Ghrayeb J., Morrison S. L., Chang N., Koprowski H. Chimeric antibodies with 17-1A-derived variable and human constant regions. Hybridoma. 1986 Jul;5 (Suppl 1):S17–S20. [PubMed] [Google Scholar]
- Takahashi N., Ueda S., Obata M., Nikaido T., Nakai S., Honjo T. Structure of human immunoglobulin gamma genes: implications for evolution of a gene family. Cell. 1982 Jun;29(2):671–679. doi: 10.1016/0092-8674(82)90183-0. [DOI] [PubMed] [Google Scholar]
- Winkelhake J. L. Immunoglobulin structure and effector functions. Immunochemistry. 1978 Sep;15(9):695–714. doi: 10.1016/0161-5890(78)90044-5. [DOI] [PubMed] [Google Scholar]