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Generation of monoclonal antibodies against soluble human T cell receptor polypeptides

Devaux, Brigitte and Bjorkman, Pamela J. and Stevenson, Christine and Greif, William and Ellio, John F. and Sagerström, Charles and Clayberger, Carol and Krensky, Alan M. and Davis, Mark M. (1991) Generation of monoclonal antibodies against soluble human T cell receptor polypeptides. European Journal of Immunology, 21 (9). pp. 2111-2119. ISSN 0014-2980. https://resolver.caltech.edu/CaltechAUTHORS:20170411-082454807

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Abstract

One approach to the diagnosis and therapy of T cell-mediated diseases is to develop reagents specific for T cell receptor (TcR) variable (V) regions. To date, however, TcR expressed on the surface of antigen-specific T lymphocytes have proven to be poorly immunogenic. As a result, few monoclonal antibodies (mAb) recognizing human variable regions are available. In this report, we have used the “phosphatidylinositol linkage” strategy to generate soluble forms of two human allogeneic TcR derived from human cytotoxic T lymphocytes (CTL) known to be specific for HLA-A2 and HLA-Aw68/HLA-Aw69, respectively. Monomeric TcR α and ß chains from the HLA-A2-specific CTL were purified in large quantities from CHO cells and each was used to immunize mice to generate mAb. In particular, the anti-β chain mAb, denoted anti-V_β13, stain a significant (≈ 5%) fraction of human peripheral blood α/β T lymphocytes, immunoprecipitate native anti-A2 TcR molecules, and activate T cells transfected with the relevant α and β chain cDNA. Anti-α chain mAb were also obtained against a constant region determinant which can immunoprecipitate detergent-solubilized polypeptides. In general, we find that immunizations with soluble protein are far superior to those with cells bearing TcR chimeras or in combination with the purified protein.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1002/eji.1830210920DOIArticle
http://onlinelibrary.wiley.com/doi/10.1002/eji.1830210920/abstractPublisherArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1991 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Manuscript Received: 29 April 1991. Funded by: HHMI and NIH.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHUNSPECIFIED
Issue or Number:9
Record Number:CaltechAUTHORS:20170411-082454807
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170411-082454807
Official Citation:Devaux, B., Bjorkman, P. J., Stevenson, C., Greif, W., Ellio, J. F., Sagerström, C., Clayberger, C., Krensky, A. M. and Davis, M. M. (1991), Generation of monoclonal antibodies against soluble human T cell receptor polypeptides. Eur. J. Immunol., 21: 2111–2119. doi:10.1002/eji.1830210920
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76498
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Apr 2017 16:59
Last Modified:03 Oct 2019 17:01

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