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-Chain Displays Intrinsic Receptor Function and Antigen Specificity1
* Institut National de la Santé et de la Recherche Médicale Unité 503, Lyon, France;
Université Claude Bernard Lyon I, Lyon, France;
Department of Immunology, University of Toronto, Sunnybrook Research Institute, Toronto, Ontario, Canada;
Ecole Normale Supérieure de Lyon, Lyon, France;
¶ Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105; and
|| Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
The C
0 alternate cassette exon is located between the J1 and C1 genes in the mouse TCR -locus. In T cells with a VDJ1 rearrangement, the C0 exon may be included in TCR transcripts (herein called TCR-C0 transcripts), potentially inserting an additional 24 aa between the V and C domains of the TCR -chain. These TCR splice isoforms may be differentially regulated after Ag activation, because we detected TCR-C0 transcripts in a high proportion (>60%) of immature and mature T cells having VDJ1 rearrangements but found a substantially reduced frequency (<35%) of TCR-C0 expression among CD8 T cells selected by Ag in vivo. To study the potential activity of the TCR-C0 splice variant, we cloned full-length TCR cDNAs by single-cell RT-PCR into retroviral expression vectors. We found that the TCR-C0 splice isoform can function during an early stage of T cell development normally dependent on TCR -chain expression. We also demonstrate that T hybridoma-derived cells expressing a TCR-C0 isoform together with the clonally associated TCR 
-chain recognize the same cognate peptide-MHC ligand as the corresponding normal TCR. This maintenance of receptor function and specificity upon insertion of the C0 peptide cassette signifies a remarkable adaptability for the TCR -chain, and our findings open the possibility that this splice isoform may function in vivo.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 M.C. is supported by a Canadian Institutes of Health Research Doctoral Research Award. D.A.A.V. and A.L.S.-W. are supported by the National Institutes of Health and the American Lebanese Syrian Associated Charities, J.C.Z.-P. is supported by a Canada Research Chair in Developmental Immunology, and the J.L.M. laboratory is supported by Institut National de la Santé et de la Recherche Médicale and La Ligue Contre le Cancer (Rhône Département, France).
2 Current address: Institut National de la Santé et de la Recherche Médicale Unité 817, Institut de Recherche sur le Cancer de Lille, Lille, France.
3 Address correspondence and reprint requests to Dr. Janet L. Maryanski at the current address: Institut National de la Santé et de la Recherche Médicale Unité 576, Hopital de l’Archet, 151 Route de Saint-Antoine de Ginestière, Boîte Postale 3079, 06202 Nice Cedex 3, France. E-mail address: maryanski{at}cervi-lyon.inserm.fr or maryanski{at}unice.fr
4 Abbreviations used in this paper: pMHC, peptides presented by MHC molecules; CSC, chondroitin sulfate c; DN, double negative; DP, double positive; i.c., intracellular; SN, supernatant; Pb, Polybrene; SP, single positive; YFP, yellow fluorescent protein.
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