title: High-sequence diversity and structural conservation in the human T-cell receptor β junctional region during thymic development.
abstract: The T-cell repertoire depends on intrathymic genetic rearrangement events in the T-cell receptor (TCR) locus, followed by positive and negative selection. The repertoire thus generated is highly diverse, but recent data indicate that the recombination of gene segments is less stochastic than previously suggested. Very little is known of the junctional complementarity determining region 3 (CDR3), which is to a large degree not germline encoded. We have analyzed the development of the human TCR β CDR3 repertoire, from the nonselected CD4(+) CD8(+) CD3(-) cells up to the fully selected CD4(+) CD8(-) thymocytes. In addition to spectratyping, a fraction of the CDR3 repertoire was sequenced and a structural in silico analysis of the CDR3 loop characteristics performed. Our data show that the thymic TCR repertoire is extremely diverse, and the effect of the selection events can be detected as a measurable loss of polyclonality in the CDR3 loop. However, the main physicochemical features of the CDR3 loop were found already at the nonselected repertoire and showed no progressive changes during the selection. Thus, the main structural characteristics of the CDR3 loop were already determined by the recombination process and not significantly affected by the extensive thymocyte death associated with selection in the thymus.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland. anni.tuulasvaara@helsinki.fi
authors.forename: Anni
authors.initials: A
authors.lastname: Tuulasvaara
authors.forename: Julie
authors.initials: J
authors.lastname: Baussand
authors.forename: Pia
authors.initials: P
authors.lastname: Laine
authors.forename: Lars
authors.initials: L
authors.lastname: Paulin
authors.forename: Jukka
authors.initials: J
authors.lastname: Salminen
authors.forename: Petri
authors.initials: P
authors.lastname: Auvinen
authors.forename: Guy
authors.initials: G
authors.lastname: Gorochov
authors.forename: T Petteri
authors.initials: TP
authors.lastname: Arstila
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002478:Cells, Cultured; D002675:Child, Preschool; D022801:Complementarity Determining Regions / Q000235:genetics*; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013950:Thymus Gland / Q000196:embryology*
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: T cells; TCR; Thymic selection