Regulation of T cell receptor (TCR)-beta locus allelic exclusion and initiation of TCR-alpha locus rearrangement in immature thymocytes by signaling through the CD3 complex.
During thymocyte differentiation, the T cell receptor (TCR)-beta genes are rearranged before the TCR-alpha genes. Immature CD4-8- double-negative thymocytes with a productive rearrangement of the TCR-beta locus are selected to continue maturation to the CD4+8+ double-positive stage, driven by signals through the pre-TCR. The signals through the pre-TCR can be synchronized by injection of mice with anti-CD3 epsilon monoclonal antibody. Using this approach, we demonstrated coordinated induction of a triad of responses in immature thymocytes: arrest of V to DJ rearrangement in the TCR-beta locus, transient down-regulation of rearrangement-activating gene (RAG)-1 and RAG-2 transcripts, and initiation of germ-line transcription of the TCR-alpha locus. These results suggest that the transition from TCR-beta to TCR-alpha locus rearrangement is controlled by signal transduction through the pre-TCR.
Levelt
C N
CN
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Wang
B
B
Ehrfeld
A
A
Terhorst
C
C
Eichmann
K
K
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018398:Homeodomain Proteins; D008215:Lymphocytes, Null / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016853:Muromonab-CD3 / Q000276:immunology / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D016853:Muromonab-CD3; D011506:Proteins; C499308:Rag2 protein, mouse; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein