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Updated: May 18, 2026
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Combined Immunofluorescence and DNA FISH on 3D-preserved Interphase Nuclei to Study Changes in 3D Nuclear Organization
Published on: February 3, 2013
Chromatin conformation governs T-cell receptor Jβ gene segment usage
Wilfred Ndifon1, Hilah Gal, Eric Shifrut
1Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Summary
Chromatin conformation influences T-cell receptor (TCR) gene segment selection, explaining biases in TCR repertoire diversity. This structural bias impacts TCR sequence frequency and sharing among individuals.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- T cells are crucial for adaptive immunity, with diverse T-cell receptors (TCRs) generated by V(D)J recombination.
- Mechanisms driving biases in TCR gene segment usage during recombination are not fully understood.
Purpose of the Study:
- To investigate the role of chromatin conformation in determining biases of T-cell receptor beta (TCRβ) gene segment usage.
- To explain the observed differences in TCR repertoire composition between mice and humans.
Main Methods:
- High-throughput TCR sequencing in murine T cells.
- Development and application of a physical model of chromatin conformation at the DJβ locus.
Main Results:
- Chromatin conformation model accurately predicts over 80% of Jβ gene segment usage biases in mice.
- The model explains interspecies differences in Jβ bias between human and mouse TCR repertoires based on genomic distances.
- A core set of highly abundant TCR sequences shared among individuals was identified, linked to their a priori recombination probability.
Conclusions:
- Chromatin conformation plays a critical role in precise T-cell receptor gene segment selection during VDJ rearrangement.
- Structural biases in TCR recombination influence repertoire diversity and the generation of public TCR sequences.
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