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Published on: October 22, 2010
Genetic modulation of T cell receptor gene segment usage during somatic recombination
F Livak1, D B Burtrum, L Rowen
1Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 08360, USA.
The Journal of Experimental Medicine
|October 18, 2000
Summary
T cell receptor gene segment usage is not random but patterned during recombination. Recombination signal sequences influence this bias, which mirrors later selection, suggesting evolved repertoire shaping.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Lymphocyte antigen receptors are generated through somatic recombination of gene segments.
- Current understanding suggests random gene segment usage during recombination, followed by protein-mediated selection.
- This process shapes the mature T lymphocyte repertoire.
Purpose of the Study:
- To investigate whether T cell receptor (TCR) D beta and J beta gene segment usage is random during recombination.
- To identify factors influencing TCR gene segment usage hierarchy.
- To compare the bias established during recombination with that resulting from protein-mediated selection.
Main Methods:
- Analysis of T cell receptor D beta and J beta gene segment usage patterns.
- Investigation of the role of flanking recombination signal sequences (RSS) in gene segment selection.
- Assessment of RSS binding affinity to recombinase and paired synaptic complex formation.
Main Results:
- TCR D beta and J beta gene segment usage is not random but exhibits a distinct pattern at the time of recombination.
- Gene segment usage hierarchy is independent of genomic proximity.
- RSS flanking sequences significantly influence gene segment usage by affecting recombinase binding and synaptic complex formation.
Conclusions:
- Recombination signal sequences play a crucial role in patterning TCR gene segment usage during V(D)J recombination.
- The bias established during recombination is similar to the repertoire bias observed after protein-mediated selection.
- RSS may have evolved to pre-bias the naive T cell repertoire towards potentially useful gene products, in addition to directing recombinase activity.
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