Diversity, functionality, and stability of the T cell repertoire derived in vivo from a single human T cell precursor.
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.
Bousso
P
P
Unité de Biologie Moléculaire du Gène, Inserm U277, 75015 Paris, France.
Wahn
V
V
Douagi
I
I
Horneff
G
G
Pannetier
C
C
Le Deist
F
F
Zepp
F
F
Niehues
T
T
Kourilsky
P
P
Fischer
A
A
de Saint Basile
G
G
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*
D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell