A natural structural variant of the mouse TCR beta-chain displays intrinsic receptor function and antigen specificity.

Published

Journal Article

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.

Full Text

Cited Authors

  • Aublin, A; Ciofani, M; Willkomm, N; Hamrouni, A; Szymczak-Workman, AL; Takahashi, T; Sandjeu, Y; Guillaume, P; Vignali, DAA; Michielin, O; Zúñiga-Pflücker, JC; Maryanski, JL

Published Date

  • December 15, 2006

Published In

Volume / Issue

  • 177 / 12

Start / End Page

  • 8587 - 8594

PubMed ID

  • 17142757

Pubmed Central ID

  • 17142757

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.177.12.8587

Language

  • eng

Conference Location

  • United States