The CDR3 regions of T cell receptor (TCR)-α and -β chains play central roles in the recognition of antigen (Ag)-MHC complex. TCR repertoire is created on the basis of Ag recognition specificity by CDR3s. To analyze the potential spectrum of TCR-α and -β to exhibit Ag specificity and generate TCR repertoire, we established hundreds of TCR transfectants bearing a single TCR-α or -β chain derived from a cytotoxic T cell (CTL) clone, RT-1, specific for HIVgp160 peptide, and randomly picked up TCR-β or -α chains. Surprisingly, one-third of such TCR-β containing random CDR3β from naive T cells of normal mice could reconstitute the antigen-reactive TCR coupling with RT-1 TCR-α. A similar dominant function of TCR-α in forming Ag-specific TCR, though low-frequency, was obtained for lymphocytic choriomeningitis virus–specific TCR. Subsequently, we generated TCR-α and/or -β transgenic (Tg) mice specific for HIVgp160 peptide, and analyzed the TCR repertoire of Ag-specific CTLs. Similar to the results from TCR reconstitution, TCR-α Tg generated CTLs with heterogeneous TCR-β, whereas TCR-β Tg-induced CTLs bearing a single TCR-α. These findings of Ag recognition with minimum involvement of CDR3β expand our understanding regarding the flexibility of the spectrum of TCR and suggest a predominant role of TCR-α chain in determining the preimmune repertoire of Ag-specific TCR.
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15 April 2002
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April 15 2002
Predominant Role of T Cell Receptor (TCR)-α Chain in Forming Preimmune TCR Repertoire Revealed by Clonal TCR Reconstitution System
Tadashi Yokosuka,
Tadashi Yokosuka
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
2Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
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Kan Takase,
Kan Takase
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
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Misao Suzuki,
Misao Suzuki
4Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan
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Yohko Nakagawa,
Yohko Nakagawa
5Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan
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Shinsuke Taki,
Shinsuke Taki
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
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Hidemi Takahashi,
Hidemi Takahashi
5Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan
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Takehiko Fujisawa,
Takehiko Fujisawa
2Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
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Hisashi Arase,
Hisashi Arase
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
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Takashi Saito
Takashi Saito
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
3Cell Signaling Team, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan
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Tadashi Yokosuka
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
2Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Kan Takase
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Misao Suzuki
4Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan
Yohko Nakagawa
5Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan
Shinsuke Taki
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Hidemi Takahashi
5Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan
Takehiko Fujisawa
2Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Hisashi Arase
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Takashi Saito
1Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
3Cell Signaling Team, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan
Address correspondence to T. Saito, Dept. of Molecular Genetics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Phone: 81-43-226-2197; Fax: 81-43-222-1791; E-mail: [email protected]
H. Arase's current address is Dept. of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143.
*
Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; Tg, transgenic.
Received:
May 14 2001
Revision Received:
February 15 2002
Accepted:
March 01 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (8): 991–1001.
Article history
Received:
May 14 2001
Revision Received:
February 15 2002
Accepted:
March 01 2002
Citation
Tadashi Yokosuka, Kan Takase, Misao Suzuki, Yohko Nakagawa, Shinsuke Taki, Hidemi Takahashi, Takehiko Fujisawa, Hisashi Arase, Takashi Saito; Predominant Role of T Cell Receptor (TCR)-α Chain in Forming Preimmune TCR Repertoire Revealed by Clonal TCR Reconstitution System . J Exp Med 15 April 2002; 195 (8): 991–1001. doi: https://doi.org/10.1084/jem.20010809
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