
Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.
Adaptive immunity depends on diverse T cell receptor repertoires generated by variable, diversity, and joining (V[D]J) recombination. Here, we define the principles by which combinatorial diversity is generated in the murine Tcra repertoire. Tcra and Tcrd gene segments share the Tcra-Tcrd locus, with interspersed Vα and Vδ segments undergoing Vδ-Dδ-Jδ rearrangement in CD4-CD8- thymocytes and then multiple rounds of Vα-Jα rearrangement in CD4+CD8+ thymocytes. We document stepwise, highly coordinated proximal-to-distal progressions of Vα and Jα use on individual Tcra alleles, limiting combinatorial diversity. This behavior is supported by an extended chromatin conformation in CD4+CD8+ thymocytes, with only nearby Vα and Jα segments contacting each other. Tcrd rearrangements can use distal Vδ segments due to a contracted Tcra-Tcrd conformation in CD4-CD8- thymocytes. These rearrangements expand the Tcra repertoire by truncating the Vα array to permit otherwise disfavored Vα-Jα combinations. Therefore, recombination events at two developmental stages with distinct chromatin conformations synergize to promote Tcra repertoire diversity.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- V(D)J Recombination
- Thymocytes
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Antigen, T-Cell, alpha-beta
- Models, Genetic
- Mice, Knockout
- Mice
- Animals
- 31 Biological sciences
- 1116 Medical Physiology
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- V(D)J Recombination
- Thymocytes
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Antigen, T-Cell, alpha-beta
- Models, Genetic
- Mice, Knockout
- Mice
- Animals
- 31 Biological sciences
- 1116 Medical Physiology