A natural structural variant of the mouse TCR beta-chain displays intrinsic receptor function and antigen specificity.
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.
Aublin
Anne
A
INSERM Unité 503, Université Claude Bernard Lyon I, Lyon, France.
Ciofani
Maria
M
Willkomm
Nancy
N
Hamrouni
Abdelbasset
A
Szymczak-Workman
Andrea L
AL
Takahashi
Tomio
T
Sandjeu
Yongoua
Y
Guillaume
Philippe
P
Vignali
Dario A A
DA
Michielin
Olivier
O
Zúñiga-Pflücker
Juan Carlos
JC
Maryanski
Janet L
JL
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D000939:Epitopes; D015321:Gene Rearrangement; D019674:Genes, T-Cell Receptor beta; D006825:Hybridomas / Q000166:cytology / Q000378:metabolism; D051379:Mice; D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
D000939:Epitopes; D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta