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Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.

ABSTRACT: 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 V? and V? segments undergoing V?-D?-J? rearrangement in CD4-CD8- thymocytes and then multiple rounds of V?-J? rearrangement in CD4+CD8+ thymocytes. We document stepwise, highly coordinated proximal-to-distal progressions of V? and J? use on individual Tcra alleles, limiting combinatorial diversity. This behavior is supported by an extended chromatin conformation in CD4+CD8+ thymocytes, with only nearby V? and J? segments contacting each other. Tcrd rearrangements can use distal V? segments due to a contracted Tcra-Tcrd conformation in CD4-CD8- thymocytes. These rearrangements expand the Tcra repertoire by truncating the V? array to permit otherwise disfavored V?-J? combinations. Therefore, recombination events at two developmental stages with distinct chromatin conformations synergize to promote Tcra repertoire diversity.

SUBMITTER: Carico ZM 

PROVIDER: S-EPMC5529038 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.

Carico Zachary M ZM   Roy Choudhury Kingshuk K   Zhang Baojun B   Zhuang Yuan Y   Krangel Michael S MS  

Cell reports 20170601 10

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 V<sub>α</sub> and V<sub>δ</sub> segments undergoing V<sub>δ</sub>-D<sub>δ</sub>-J<sub>δ</sub> rearrangement in CD4<sup>-</sup>CD8<sup>-</sup> thymocytes and then multiple rounds of V<su  ...[more]

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