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TCR-delta gene rearrangement and selection during fetal thymocyte development
O M Wilbert1, J Weber-Arden, D Kabelitz
1Department of Immunology, Paul Ehrlich Institute, Langen, Germany.
Journal of Immunology (Baltimore, Md. : 1950)
|October 8, 1997
Summary
T-cell receptor (TCR) delta-chain gene rearrangements show evolutionary selection. Cellular selection, not random rearrangement, appears crucial for gamma delta T cell maturation in the thymus.
Area of Science:
- Immunology
- Molecular Biology
- Developmental Biology
Background:
- T-cell receptor (TCR) delta-chain gene rearrangements are critical for T-cell development.
- Understanding the selection pressures on TCR delta-chain rearrangements is key to deciphering T-cell lineage commitment.
Purpose of the Study:
- To analyze TCR delta-chain gene rearrangements during thymic ontogeny.
- To investigate the role of evolutionary and cellular selection in gamma delta T-cell development.
Main Methods:
- Analysis of VDJ delta junctional sequences in fetal and neonatal thymocytes.
- Comparison of TCR delta-chain gene rearrangements in wild-type and C delta-mutant mice.
- Assessment of in-frame transcript frequencies in genomic DNA and transcripts.
Main Results:
- Highly conserved VDJ delta junctional sequences of the V7 subfamily were observed in both wild-type and mutant mice.
- A reduced frequency of in-frame transcripts (61%) was found in C delta-mutant mice compared to wild-type (88%), suggesting cellular selection.
- No significant difference in productive rearrangement frequency was observed in genomic DNA between mutant (26%) and wild-type (31%) mice.
Conclusions:
- Evolutionary selection acts at the DNA rearrangement level for TCR delta-chain V7 subfamily.
- Cellular selection, rather than random rearrangement, appears to be a critical factor in the thymic maturation of gamma delta T cells.
- Findings provide insights into models of alpha beta/gamma delta T-cell lineage commitment.