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Highly diverse TCRα chain repertoire of pre‐immune CD8 + T cells reveals new insights in gene recombination
Author(s) -
Genolet Raphael,
Stevenson Brian J,
Farinelli Laurent,
Østerås Magne,
Luescher Immanuel F
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.48
Subject(s) - biology , t cell receptor , recombination , repertoire , gene , genetics , gene rearrangement , immune system , cd8 , t cell , physics , acoustics
Although the T‐cell receptor αδ (TCRαδ) locus harbours large libraries of variable (TRAV) and junctional (TRAJ) gene segments, according to previous studies the TCRα chain repertoire is of limited diversity due to restrictions imposed by sequential coordinate TRAV‐TRAJ recombinations. By sequencing tens of millions of TCRα chain transcripts from naive mouse CD8 + T cells, we observed a hugely diverse repertoire, comprising nearly all possible TRAV‐TRAJ combinations. Our findings are not compatible with sequential coordinate gene recombination, but rather with a model in which contraction and DNA looping in the TCRαδ locus provide equal access to TRAV and TRAJ gene segments, similarly to that demonstrated for IgH gene recombination. Generation of the observed highly diverse TCRα chain repertoire necessitates deletion of failed attempts by thymic‐positive selection and is essential for the formation of highly diverse TCRαβ repertoires, capable of providing good protective immunity.