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- Title
New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling.
- Authors
Dik, Willem A; Pike-Overzet, Karin; Weerkamp, Floor; de Ridder, Dick; de Haas, Edwin F E; Baert, Miranda R M; van der Spek, Peter; Koster, Esther E L; Reinders, Marcel J T; van Dongen, Jacques J M; Langerak, Anton W; Staal, Frank J T
- Abstract
To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human T cell development, we analyzed TCR gene rearrangements by quantitative PCR analysis in nine consecutive T cell developmental stages, including CD34+ lin- cord blood cells as a reference. The same stages were used for gene expression profiling using DNA microarrays. We show that TCR loci rearrange in a highly ordered way (TCRD-TCRG-TCRB-TCRA) and that the initiating Ddelta2-Ddelta3 rearrangement occurs at the most immature CD34+CD38-CD1a- stage. TCRB rearrangement starts at the CD34+CD38+CD1a- stage and complete in-frame TCRB rearrangements were first detected in the immature single positive stage. TCRB rearrangement data together with the PTCRA (pTalpha) expression pattern show that human TCRbeta-selection occurs at the CD34+CD38+CD1a+ stage. By combining the TCR rearrangement data with gene expression data, we identified candidate factors for the initiation/regulation of TCR recombination. Our data demonstrate that a number of key events occur earlier than assumed previously; therefore, human T cell development is much more similar to murine T cell development than reported before.
- Publication
The Journal of experimental medicine, 2005, Vol 201, Issue 11, p1715
- ISSN
0022-1007
- Publication type
Journal Article
- DOI
10.1084/jem.20042524