Chimaeric monoclonal antibodies encoded by the human VH26 gene from naive transgenic mice display a wide range of antigen binding specificities

Harmer, I., Mageed, R.A., Kaminski, A., Charles, P., Bruggemann, M. and Mackworth-Young, C.G. 1996. Chimaeric monoclonal antibodies encoded by the human VH26 gene from naive transgenic mice display a wide range of antigen binding specificities. Immunology. 88 (2), pp. 174-182. https://doi.org/10.1111/j.1365-2567.1996.tb00002.x

TitleChimaeric monoclonal antibodies encoded by the human VH26 gene from naive transgenic mice display a wide range of antigen binding specificities
AuthorsHarmer, I., Mageed, R.A., Kaminski, A., Charles, P., Bruggemann, M. and Mackworth-Young, C.G.
Abstract

To elucidate the molecular basis for the ability of antibodies encoded by the human VH26 heavy-chain variable region gene to react with diverse antigens, we have generated 34 hybridomas secreting chimaeric monoclonal antibodies (human μ heavy chain/mouse light chains) from transgenic mice. The transgenic mice carry an immunoglobulin minilocus containing the human VH26 gene, human DH and JH gene segments, and genes encoding the human Cμ region. The minilocus in these animals undergoes functional rearrangement resulting in the production of chimaeric antibodies in which human μ heavy chains utilizing the VH26 gene are paired with mouse k or Λ light chains. The hybridomas described in this study were generated from naïve animals and were selected solely on the basis of human μ-chain expression. The antibodies described have covalently attached mouse light chains and are multimeric in structure. The binding properties of the antibodies were examined using a panel of both self- and foreign antigens using enzyme-linked immunosorbent assays, agglutination or radio-immunoprecipitation assays and immunofluorescence. Chimaeric immunoglobulins from 21 of the 34 hybridoma clones (61·7%) reacted with one or more antigens, of which 13 (38·2%) reacted with more than two antigens. These studies demonstrate that the VH26 gene, in combination with human DH and JH gene segments, and mouse light-chain genes, is able to encode antibodies with a wide range of ligand-binding specificities. These findings have important implications in the context of the possible origins of autoantibodies encoded by VH26 which may play a role in the pathogenesis of a number of autoimmune conditions.

JournalImmunology
Journal citation88 (2), pp. 174-182
ISSN0019-2805
Year1996
PublisherWiley
Digital Object Identifier (DOI)https://doi.org/10.1111/j.1365-2567.1996.tb00002.x

Related outputs

Molecular characterization of the variable domains of an αIIbβ3-specific immunoglobulin M κ platelet cold agglutinin in a follicular lymphoma patient with treatment refractory autoimmune thrombocytopenia: idiotypic overlap between αIIbβ3 integrin antibodies
Jennings, N.S., Harmer, I., Campbell, K., Stafford, P., Smith, G.A., Metcalfe, P., Benton, M.A., Marsh, J.C.W. and Ouwehand, W.H. 2007. Molecular characterization of the variable domains of an αIIbβ3-specific immunoglobulin M κ platelet cold agglutinin in a follicular lymphoma patient with treatment refractory autoimmune thrombocytopenia: idiotypic overlap between αIIbβ3 integrin antibodies. Transfusion. 47 (3), pp. 499-510. https://doi.org/10.1111/j.1537-2995.2006.01142.x

Production of calmodulin-tagged proteins in Drosophila Schneider S2 cells: a novel system for antigen production and phage antibody isolation
Jennings, N.S., Smethurst, P.A., Knight, G., O'Connor, M.N., Joutsi-Korhonen, L., Stafford, P., Stephens, J., Garner, S.F., Harmer, I., Farndale, R.W., Watkins, N.A. and Ouwehand, W.H. 2006. Production of calmodulin-tagged proteins in Drosophila Schneider S2 cells: a novel system for antigen production and phage antibody isolation. Journal of Immunological Methods. 316 (1-2), pp. 75-83. https://doi.org/10.1016/j.jim.2006.08.003

Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms
Watkins, N.A., O'Connor, M.N., Rankin, A., Jennings, N.S., Wilson, E., Harmer, I., Davies, L., Smethurst, P.A., Dudbridge, F., Farndale, R.W. and Ouwehand, W.H. 2006. Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms. Journal of Thrombosis and Haemostasis. 4 (6), pp. 1197-1205. https://doi.org/10.1111/j.1538-7836.2006.01937.x

Platelet integrin α 2 I-domain specific antibodies produced via domain specific DNA vaccination combined with variable gene phage display
Hughes, D.L., Stafford, P., Hamaia, S.W., Harmer, I., Schoolmeester, A., Deckmyn, H., Farndale, R.W., Ouwehand, W.H. and Watkins, N.A. 2005. Platelet integrin α 2 I-domain specific antibodies produced via domain specific DNA vaccination combined with variable gene phage display. Thrombosis and Haemostasis. 94 (16), pp. 1318-1326. https://doi.org/10.1160/TH05-06-0410

The role of antigen in the selection of the human V3-23 immunoglobulin heavy chain variable region gene
Mackworth-Young, C.G., Harmer, I. and Mageed, R.A. 2003. The role of antigen in the selection of the human V3-23 immunoglobulin heavy chain variable region gene. Clinical and Experimental Immunology. 134 (3), pp. 420-425. https://doi.org/10.1111/j.1365-2249.2003.02319.x

Recent progress in the understanding of B-cell functions in autoimmunity
Porakishvili, N., Mageed, R.A., Jamin, C., Pers, J.O., Kulikova, N., Renaudineau, Y., Lydyard, P.M. and Youinou, P.Y. 2001. Recent progress in the understanding of B-cell functions in autoimmunity. Scandinavian Journal of Immunology. 54 (1-2), pp. 30-38. https://doi.org/10.1046/j.1365-3083.2001.00950.x

Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of VHCDR3 and residues intrinsic to the heavy chain variable region
Mageed, R.A., Harmer, I., Wynn, S.L., Moyes, S.P., Maziak, B.R., Bruggemann, M. and Mackworth-Young, C.G. 2001. Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of VHCDR3 and residues intrinsic to the heavy chain variable region. Clinical and Experimental Immunology. 123 (1), pp. 1-8. https://doi.org/10.1046/j.1365-2249.2001.01380.x

The BH1 idiotype defines a population of anticardiolipin antibodies closely associated with the antiphospholipid syndrome
Mason, A.N., Harmer, I. and Mackworth-Young, C.G. 1999. The BH1 idiotype defines a population of anticardiolipin antibodies closely associated with the antiphospholipid syndrome. Lupus. 8 (3), pp. 234-239. https://doi.org/10.1191/096120399678847687

Phospholipid binding specificities and idiotype expression of hybridoma derived monoclonal autoantibodies from splenic cells of patients with systemic lupus erythematosus
Ravirajan, C.T., Harmer, I., McNally, T., Hohmann, A., Mackworth-Young, C.G. and Isenberg D, A. 1995. Phospholipid binding specificities and idiotype expression of hybridoma derived monoclonal autoantibodies from splenic cells of patients with systemic lupus erythematosus. Annals of the Rheumatic Diseases. 54 (6), pp. 471-476. https://doi.org/10.1136/ard.54.6.471

Endothelium-derived haemostatic factors and the antiphospholipid syndrome
Mackworth-Young, C.G., Andreotti, F., Harmer, I., Loizou, S., Pottinger, B.E., Pearson, J.D., Maseri, A. and Walport M, J. 1995. Endothelium-derived haemostatic factors and the antiphospholipid syndrome. British Journal of Rheumatology. 34, pp. 201-206.

A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded
Harmer, I., Loizou, S., Thompson, K., So, A.K., Walport M, J., Mackworth-Young, C.G. and A. K. So 1995. A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded. Arthritis and Rheumatism. 38, pp. 1068-1076. https://doi.org/10.1002/art.1780380808

The FITC-anti-FITC system is a sensitive alternative to biotin-streptavidin in ELISA
Harmer, I. and Samuel, D. 1989. The FITC-anti-FITC system is a sensitive alternative to biotin-streptavidin in ELISA. Journal of Immunological Methods. 122 (1), pp. 115-121. https://doi.org/10.1016/0022-1759(89)90341-4

Structural and idiotypic relationships between monoclonal antibodies specific for IgG1 (Fc) subclass epitopes
Harmer, I. and Jefferis, R. 1988. Structural and idiotypic relationships between monoclonal antibodies specific for IgG1 (Fc) subclass epitopes. Biochemical Society Transactions. 16 (5), pp. 747-8. https://doi.org/10.1042/bst0160747a

Permalink - https://westminsterresearch.westminster.ac.uk/item/9v690/chimaeric-monoclonal-antibodies-encoded-by-the-human-vh26-gene-from-naive-transgenic-mice-display-a-wide-range-of-antigen-binding-specificities


Share this

Usage statistics

164 total views
0 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.