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Predominant Role of T Cell Receptor (TCR)- Chain in Forming Preimmune TCR Repertoire Revealed by Clonal TCR Reconstitution System

Tadashi Yokosuka^1,2, Kan Takase¹, Misao Suzuki⁴, Yohko Nakagawa⁵, Shinsuke Taki¹, Hidemi Takahashi⁵, Takehiko Fujisawa², Hisashi Arase¹ and Takashi Saito^1,3

¹ Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
² Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
³ Cell Signaling Team, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan
⁴ Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan
⁵ Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, 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: saito{at}med.m.chiba-u.ac.jp

The CDR3 regions of T cell receptor (TCR)- and -ß 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- and -ß to exhibit Ag specificity and generate TCR repertoire, we established hundreds of TCR transfectants bearing a single TCR- or -ß chain derived from a cytotoxic T cell (CTL) clone, RT-1, specific for HIVgp160 peptide, and randomly picked up TCR-ß or - chains. Surprisingly, one-third of such TCR-ß containing random CDR3ß from naive T cells of normal mice could reconstitute the antigen-reactive TCR coupling with RT-1 TCR-. A similar dominant function of TCR- in forming Ag-specific TCR, though low-frequency, was obtained for lymphocytic choriomeningitis virus–specific TCR. Subsequently, we generated TCR- and/or -ß transgenic (Tg) mice specific for HIVgp160 peptide, and analyzed the TCR repertoire of Ag-specific CTLs. Similar to the results from TCR reconstitution, TCR- Tg generated CTLs with heterogeneous TCR-ß, whereas TCR-ß Tg-induced CTLs bearing a single TCR-. These findings of Ag recognition with minimum involvement of CDR3ß expand our understanding regarding the flexibility of the spectrum of TCR and suggest a predominant role of TCR- chain in determining the preimmune repertoire of Ag-specific TCR.

Key Words: antigen recognition • CDR3 • CTL • HIV gp160 • selection

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