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

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Jun 8

PMID 28591585

Citations 20

Authors

Zachary M Carico

Kingshuk Roy Choudhury

Baojun Zhang

Yuan Zhuang

Michael S Krangel

Affiliations

Soon will be listed here.

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 CD4CD8 thymocytes and then multiple rounds of V-J rearrangement in CD4CD8 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 CD4CD8 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 CD4CD8 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.

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