title: Diversity, functionality, and stability of the T cell repertoire derived in vivo from a single human T cell precursor.
abstract: In this report, we have analyzed the human T cell repertoire derived in vivo from a single T cell precursor. A unique case of X-linked severe combined immunodeficiency in which a reverse mutation occurred in an early T cell precursor was analyzed to this end. It was determined that at least 1,000 T cell clones with unique T cell receptor-beta sequences were generated from this precursor. This diversity seems to be stable over time and provides protection from infections in vivo. A similar estimation was obtained in an in vitro murine model of T cell generation from a single cell precursor. Overall, our results document the large diversity potential of T cell precursors and provide a rationale for gene therapy of the block of T cell development.
authors.affiliation: Unité de Biologie Moléculaire du Gène, Inserm U277, 75015 Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Bousso
authors.forename: V
authors.initials: V
authors.lastname: Wahn
authors.forename: I
authors.initials: I
authors.lastname: Douagi
authors.forename: G
authors.initials: G
authors.lastname: Horneff
authors.forename: C
authors.initials: C
authors.lastname: Pannetier
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: F
authors.initials: F
authors.lastname: Zepp
authors.forename: T
authors.initials: T
authors.lastname: Niehues
authors.forename: P
authors.initials: P
authors.lastname: Kourilsky
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: G
authors.initials: G
authors.lastname: de Saint Basile
mesh_terms: D002675:Child, Preschool; D002999:Clone Cells; D022801:Complementarity Determining Regions; D005434:Flow Cytometry; D015321:Gene Rearrangement / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology; D013234:Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell