HPRT mutations, TCR gene rearrangements, and HTLV-1 integration sites define in vivo T-cell clonal lineages.
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.
Allegretta
Mark
M
Department of Pathology, University of Vermont, Burlington, Vermont 05405, USA.
Ardell
Stephanie K
SK
Sullivan
Linda M
LM
Jacobson
Steven
S
Mortreux
Franck
F
Wattel
Eric
E
Albertini
Richard J
RJ
D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D017931:DNA Primers; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008957:Models, Genetic; D015336:Molecular Probe Techniques; D009154:Mutation / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000201:enzymology*; D016662:Virus Integration / Q000235:genetics*
D017931:DNA Primers; D007041:Hypoxanthine Phosphoribosyltransferase