HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Annenkov, A. E. Articles by Chernajovsky, Y. Search for Related Content PubMed PubMed Citation Articles by Annenkov, A. E. Articles by Chernajovsky, Y.

Loss of Original Antigenic Specificity in T Cell Hybridomas Transduced with a Chimeric Receptor Containing Single-Chain Fv of an Anti-Collagen Antibody and FcRI-Signaling Subunit¹

Alexander E. Annenkov^*, Sasha P. Moyes^*, Zelig Eshhar, Rizgar A. Mageed^* and Yuti Chernajovsky^2,*

^* Kennedy Institute of Rheumatology, London, United Kingdom; and Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

T cell hybridomas HCQ6 and MD.45 acquired Ab-type specificity to collagen type II, when engrafted with a chimeric cell surface receptor, scC2Fv/, which includes the single-chain Fv domain (scFv) of the anti-collagen type II mAb C2 and the signaling subunit of the FcRI. When transduced into MD.45 cells, scC2Fv/ or its mutated form lacking immunoreceptor tyrosine-based activation motif (ITAM), scC2Fv/IC^-, formed mainly homodimers. A small proportion of these molecules formed heterodimers with endogenous CD3 in these hybridoma cells. By contrast, in HCQ6 cells, the majority of scC2Fv/ and scC2Fv/IC^- molecules formed heterodimers with CD3, and only a small proportion of them was expressed as homodimers. Stimulation with plastic-immobilized collagen induced IL-2 production in scC2Fv/-transduced MD.45 cells, but not in MD.45 cells transduced with the ITAM-less chimera scC2Fv/IC^-. HCQ6 cells transduced with scC2Fv/ responded to plastic-bound collagen. Due to the high content of CD3-associated chimeras, HCQ6 cells transduced with the ITAM-less scC2Fv/IC^- chimera were also responsive to plastic-bound collagen. When cells were stimulated with collagen in solution, MD.45 cells transduced with scC2Fv/ produced IL-2, whereas transduced HCQ6 cells were unresponsive, hence suggesting that the ability of cells transduced with scC2Fv chimeras to respond to soluble collagen correlated with predominant expression of divalent scC2Fv/ homodimers, but not monovalent scC2Fv/-CD3 or scC2Fv/IC^--CD3 heterodimers. Of interest, expression of CD3 subunits in hybridomas transduced with scC2Fv chimeras was reduced, resulting in decreased response to cognate Ags.

This article has been cited by other articles:

				J. M. Clark, A. E. Annenkov, M. Panesar, P. Isomaki, Y. Chernajovsky, and A. P. Cope T cell receptor {zeta} reconstitution fails to restore responses of T cells rendered hyporesponsive by tumor necrosis factor {alpha} PNAS, February 10, 2004; 101(6): 1696 - 1701. [Abstract] [Full Text] [PDF]

				A. E. Annenkov, G. M. Daly, T. Brocker, and Y. Chernajovsky Clustering of immunoreceptor tyrosine-based activation motif-containing signalling subunits in CD4+ T cells is an optimal signal for IFN-{gamma} production, but not for the production of IL-4 Int. Immunol., May 1, 2003; 15(5): 665 - 677. [Abstract] [Full Text] [PDF]

				P. Isomaki, M. Panesar, A. Annenkov, J. M. Clark, B. M. J. Foxwell, Y. Chernajovsky, and A. P. Cope Prolonged Exposure of T Cells to TNF Down-Regulates TCR{{zeta}} and Expression of the TCR/CD3 Complex at the Cell Surface J. Immunol., May 1, 2001; 166(9): 5495 - 5507. [Abstract] [Full Text] [PDF]

				Y. Chernajovsky Gene transfer as therapy for rheumatoid arthritis: why, what and how? Rheumatology, September 1, 1999; 38(9): 804 - 806. [Full Text] [PDF]