http://hdl.handle.net/1765/8406

New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling


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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.



Keywords


Automatically Extracted Terms
  • rearrangement
  • t cell development
  • stage
  • analysis
  • development
  • cluster
  • expression
  • j rearrangements
  • recombination
  • subset
  • level
  • thymocyte
  • probe
  • van dongen
  • tcra rearrangement
  • t cells
  • segment
  • www.jem.org
  • receptor
  • tcra rearrangements


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