HPRT mutations, TCR gene rearrangements, and HTLV-1 integration sites define in vivo T-cell clonal lineages.
Résumé
HPRT mutations in vivo in human T-lymphocytes are useful probes for mechanistic investigations. Molecular analyses of isolated mutants reveal their underlying mutational changes as well as the T-cell receptor (TCR) gene rearrangements present in the cells in question. The latter provide temporal reference points for other perturbations in the in vivo clones as well as evidence of clonal relationships among mutant isolates. Immunological studies and investigations of genomic instability have benefited from such analyses. A method is presented describing a T-cell lineage analysis in a patient with HTLV-1 infection. Lineage reconstruction of an in vivo proliferating HPRT mutant clone allows timing of the integration event to a postthymic differentiated cell prior to the occurrence of HPRT mutations.
Mots clés
Cell Differentiation/genetics
Cell Lineage/*genetics
DNA Primers
Flow Cytometry
Gene Rearrangement
T-Lymphocyte/*genetics
Human T-lymphotropic virus 1/*genetics
Humans
Hypoxanthine Phosphoribosyltransferase/*genetics
Models
Genetic
Molecular Probe Techniques
Mutation/*genetics
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes/*enzymology
Virus Integration/*genetics