Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.
| Autor: | Dauphars DJ; Department of Immunology, Duke University Medical Center, Durham, NC., Mihai A; Department of Immunology, Duke University Medical Center, Durham, NC., Wang L; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC., Zhuang Y; Department of Immunology, Duke University Medical Center, Durham, NC., Krangel MS; Department of Immunology, Duke University Medical Center, Durham, NC. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of experimental medicine [J Exp Med] 2022 Feb 07; Vol. 219 (2). Date of Electronic Publication: 2021 Dec 15. |
| DOI: | 10.1084/jem.20211581 |
| Abstrakt: | The Tcra repertoire is generated by multiple rounds of Vα-Jα rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens primary Vα use to diversify the Tcra repertoire in mice. We reveal that use of Trav15-dv6 family V gene segments in Tcrd recombination imparts diversity in the Tcra repertoire by instigating use of central and distal Vα segments. Moreover, disruption of the regions containing these genes and their cis-regulatory elements identifies the Trav15-dv6 family as being responsible for driving central and distal Vα recombinations beyond their roles as substrates for Tcrd recombination. Our study demonstrates an indispensable role for Tcrd recombination in general, and the Trav15-dv6 family in particular, in the generation of a combinatorially diverse Tcra repertoire. Competing Interests: Disclosures: The authors declare no competing interests exist. (© 2021 Dauphars et al.) |
| Databáze: | MEDLINE |
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