Article: article from journal or magazin.
A natural structural variant of the mouse TCR beta-chain displays intrinsic receptor function and antigen specificity.
Journal of immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
The Cbeta0 alternate cassette exon is located between the Jbeta1 and Cbeta1 genes in the mouse TCR beta-locus. In T cells with a VDJbeta1 rearrangement, the Cbeta0 exon may be included in TCRbeta transcripts (herein called TCRbeta-Cbeta0 transcripts), potentially inserting an additional 24 aa between the V and C domains of the TCR beta-chain. These TCRbeta splice isoforms may be differentially regulated after Ag activation, because we detected TCRbeta-Cbeta0 transcripts in a high proportion (>60%) of immature and mature T cells having VDJbeta1 rearrangements but found a substantially reduced frequency (<35%) of TCRbeta-Cbeta0 expression among CD8 T cells selected by Ag in vivo. To study the potential activity of the TCRbeta-Cbeta0 splice variant, we cloned full-length TCR cDNAs by single-cell RT-PCR into retroviral expression vectors. We found that the TCRbeta-Cbeta0 splice isoform can function during an early stage of T cell development normally dependent on TCR beta-chain expression. We also demonstrate that T hybridoma-derived cells expressing a TCRbeta-Cbeta0 isoform together with the clonally associated TCR alpha-chain recognize the same cognate peptide-MHC ligand as the corresponding normal alphabetaTCR. This maintenance of receptor function and specificity upon insertion of the Cbeta0 peptide cassette signifies a remarkable adaptability for the TCR beta-chain, and our findings open the possibility that this splice isoform may function in vivo.
Animals, Cell Line, Cloning, Molecular, Epitopes, Gene Rearrangement, Genes, T-Cell Receptor beta, Hybridomas/cytology, Hybridomas/metabolism, Mice, Protein Isoforms, Receptors, Antigen, T-Cell, alpha-beta/chemistry, Receptors, Antigen, T-Cell, alpha-beta/genetics, T-Lymphocytes/cytology, T-Lymphocytes/metabolism
Web of science
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