| First Author | Carico ZM | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 10 | Pages | 2157-2173 |
| PubMed ID | 28591585 | Mgi Jnum | J:254334 |
| Mgi Id | MGI:6103100 | Doi | 10.1016/j.celrep.2017.05.045 |
| Citation | Carico ZM, et al. (2017) Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire. Cell Rep 19(10):2157-2173 |
| abstractText | 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 Valpha and Vdelta segments undergoing Vdelta-Ddelta-Jdelta rearrangement in CD4(-)CD8(-) thymocytes and then multiple rounds of Valpha-Jalpha rearrangement in CD4(+)CD8(+) thymocytes. We document stepwise, highly coordinated proximal-to-distal progressions of Valpha and Jalpha use on individual Tcra alleles, limiting combinatorial diversity. This behavior is supported by an extended chromatin conformation in CD4(+)CD8(+) thymocytes, with only nearby Valpha and Jalpha segments contacting each other. Tcrd rearrangements can use distal Vdelta segments due to a contracted Tcra-Tcrd conformation in CD4(-)CD8(-) thymocytes. These rearrangements expand the Tcra repertoire by truncating the Valpha array to permit otherwise disfavored Valpha-Jalpha combinations. Therefore, recombination events at two developmental stages with distinct chromatin conformations synergize to promote Tcra repertoire diversity. |
