New Insights on Human T Cell Development by Quantitative T Cell Receptor Gene Rearrangement Studies and Gene Expression Profiling

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2005 Jun 2

PMID 15928199

Citations 146

Authors

Willem A Dik

Karin Pike-Overzet

Floor Weerkamp

Dick de Ridder

Edwin F E de Haas

Miranda R M Baert

Peter van der Spek

Esther E L Koster

Marcel J T Reinders

Jacques J M van Dongen

Anton W Langerak

Frank J T Staal

Affiliations

Soon will be listed here.

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.

Citing Articles

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Dual-Approach Co-expression Analysis Framework (D-CAF) Enables Identification of Novel Circadian Regulation From Multi-Omic Timeseries Data.

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