We found the TCR variant population was increased on average 2x in AT heterozygotes (vs 10x in homozygotes) compared with controls, and naïve CD4(+) T lymphocytes were reduced on average 0.5x (vs 0.1x in homozygotes).
We have modified this PCR method using total genomic DNA from the mononuclear cells in peripheral blood samples to increase specificity and to allow direct sequencing of the translocation junction that results from the recombination between the GV1 and BJ1 families of TCR genes in 25 examples from 11 individuals (three adults, one child, six newborns, and one ataxia telangiectasia (AT) patient).
These data show that formation of hybrid TCR genes is restricted to T-cells in vivo, and occurs at a very low frequency, if at all, in proliferating T-cells in vitro, and with an increased frequency in patients with ataxia telangiectasia.
Ataxia telangiectasia (A-T) is an inherited, recessive, cancer-prone disease with associated immunodeficiency and chromosome abnormalities involving TCR loci.
In this paper, using polymerase chain reaction (PCR), we demonstrated the occurrence of hybrid genes formed by interlocus recombination between T cell receptor gamma (TCR-gamma) variable (V) regions and TCR-beta joining (J) regions in the peripheral blood lymphocytes (PBL) from normal individuals and patients with ataxia-telangiectasia (AT).