title: Highly diverse TCRα chain repertoire of pre-immune CD8⁺ T cells reveals new insights in gene recombination.
abstract: 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.
authors.affiliation: Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Genolet
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Stevenson
authors.forename: Laurent
authors.initials: L
authors.lastname: Farinelli
authors.forename: Magne
authors.initials: M
authors.lastname: Osterås
authors.forename: Immanuel F
authors.initials: IF
authors.lastname: Luescher
mesh_terms: D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011995:Recombination, Genetic / Q000276:immunology*