Highly diverse TCR? chain repertoire of pre-immune CD8? T cells reveals new insights in gene recombination.

ABSTRACT: Although the T-cell receptor ?? (TCR??) locus harbours large libraries of variable (TRAV) and junctional (TRAJ) gene segments, according to previous studies the TCR? chain repertoire is of limited diversity due to restrictions imposed by sequential coordinate TRAV-TRAJ recombinations. By sequencing tens of millions of TCR? 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 TCR?? locus provide equal access to TRAV and TRAJ gene segments, similarly to that demonstrated for IgH gene recombination. Generation of the observed highly diverse TCR? chain repertoire necessitates deletion of failed attempts by thymic-positive selection and is essential for the formation of highly diverse TCR?? repertoires, capable of providing good protective immunity.

SUBMITTER: Genolet R 

PROVIDER: S-EPMC3321212 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature