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Recombinant antibodies with MHC-restricted, peptide-specific, T-cell receptor-like specificity: new tools to study antigen presentation and TCR-peptide-MHC interactions.
J Mol Recognit 2003 Sep-Oct; 16(5):324-32JM

Abstract

The advent in recent years of the application of tetrameric arrays of class I peptide-MHC complexes now enables us to detect and study rare populations of antigen-specific CD8+ T cells. However, available methods cannot visualize or determine the number and distribution of these TCR ligands on individual cells or detect antigen-presenting cells (APCs) in tissues. Here we describe a new approach that enables study of human class I peptide-MHC ligand-presentation as well as TCR-peptide-MHC interactions. Such studies are facilitated by applying novel tools in the form of peptide-specific, HLA-A2-restricted human recombinant antibodies directed toward a large variety of tumor-associated as well as viral T-cell epitope peptides. Using a large human antibody phage display library, a large panel of recombinant antibodies that are specific for a particular peptide-MHC class I complex in a peptide-dependent, MHC-restricted manner was isolated. These antibodies were used to directly visualize the specific MHC-peptide complex on tumor cells, antigen-presenting cells or virus-infected cells by flow cytometry. They enabled direct quantitation of the number of MHC-peptide complexes as well as in situ detection of the complex on the surface of APCs after naturally occurring active intracellular processing of the cognate antigen. These studies will enable also the development of a new class of targeting molecules to deliver drugs or toxins to tumor or virus-infected cells. Thus, we demonstrate our ability to transform the unique fine specificity but low intrinsic affinity of TCRs into high-affinity soluble antibody molecules endowed with a TCR-like specificity toward human tumor or viral epitopes. These molecules may prove to be crucial useful tools for studying MHC class I antigen presentation in health and disease as well as for therapeutic purposes in cancer, infectious diseases and autoimmune disorders.

Authors+Show Affiliations

Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

14523945

Citation

Cohen, Cyril J., et al. "Recombinant Antibodies With MHC-restricted, Peptide-specific, T-cell Receptor-like Specificity: New Tools to Study Antigen Presentation and TCR-peptide-MHC Interactions." Journal of Molecular Recognition : JMR, vol. 16, no. 5, 2003, pp. 324-32.
Cohen CJ, Denkberg G, Lev A, et al. Recombinant antibodies with MHC-restricted, peptide-specific, T-cell receptor-like specificity: new tools to study antigen presentation and TCR-peptide-MHC interactions. J Mol Recognit. 2003;16(5):324-32.
Cohen, C. J., Denkberg, G., Lev, A., Epel, M., & Reiter, Y. (2003). Recombinant antibodies with MHC-restricted, peptide-specific, T-cell receptor-like specificity: new tools to study antigen presentation and TCR-peptide-MHC interactions. Journal of Molecular Recognition : JMR, 16(5), pp. 324-32.
Cohen CJ, et al. Recombinant Antibodies With MHC-restricted, Peptide-specific, T-cell Receptor-like Specificity: New Tools to Study Antigen Presentation and TCR-peptide-MHC Interactions. J Mol Recognit. 2003;16(5):324-32. PubMed PMID: 14523945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant antibodies with MHC-restricted, peptide-specific, T-cell receptor-like specificity: new tools to study antigen presentation and TCR-peptide-MHC interactions. AU - Cohen,Cyril J, AU - Denkberg,Galit, AU - Lev,Avital, AU - Epel,Malka, AU - Reiter,Yoram, PY - 2003/10/3/pubmed PY - 2004/6/21/medline PY - 2003/10/3/entrez SP - 324 EP - 32 JF - Journal of molecular recognition : JMR JO - J. Mol. Recognit. VL - 16 IS - 5 N2 - The advent in recent years of the application of tetrameric arrays of class I peptide-MHC complexes now enables us to detect and study rare populations of antigen-specific CD8+ T cells. However, available methods cannot visualize or determine the number and distribution of these TCR ligands on individual cells or detect antigen-presenting cells (APCs) in tissues. Here we describe a new approach that enables study of human class I peptide-MHC ligand-presentation as well as TCR-peptide-MHC interactions. Such studies are facilitated by applying novel tools in the form of peptide-specific, HLA-A2-restricted human recombinant antibodies directed toward a large variety of tumor-associated as well as viral T-cell epitope peptides. Using a large human antibody phage display library, a large panel of recombinant antibodies that are specific for a particular peptide-MHC class I complex in a peptide-dependent, MHC-restricted manner was isolated. These antibodies were used to directly visualize the specific MHC-peptide complex on tumor cells, antigen-presenting cells or virus-infected cells by flow cytometry. They enabled direct quantitation of the number of MHC-peptide complexes as well as in situ detection of the complex on the surface of APCs after naturally occurring active intracellular processing of the cognate antigen. These studies will enable also the development of a new class of targeting molecules to deliver drugs or toxins to tumor or virus-infected cells. Thus, we demonstrate our ability to transform the unique fine specificity but low intrinsic affinity of TCRs into high-affinity soluble antibody molecules endowed with a TCR-like specificity toward human tumor or viral epitopes. These molecules may prove to be crucial useful tools for studying MHC class I antigen presentation in health and disease as well as for therapeutic purposes in cancer, infectious diseases and autoimmune disorders. SN - 0952-3499 UR - https://www.unboundmedicine.com/medline/citation/14523945/Recombinant_antibodies_with_MHC_restricted_peptide_specific_T_cell_receptor_like_specificity:_new_tools_to_study_antigen_presentation_and_TCR_peptide_MHC_interactions_ L2 - https://doi.org/10.1002/jmr.640 DB - PRIME DP - Unbound Medicine ER -