Characterization of transcripts from unrearranged V alpha 8 genes in the thymus.

Abstract

The genes that encode the alpha- and beta-chains of the TCR undergo programmed rearrangement during differentiation of a T cell in the thymus, but it is not known what controls the order and specificity of the rearrangement event. By analogy with Ig genes, it is possible that transcription of an unrearranged V region gene may be necessary for "access" of the recombinase. To begin to address this issue, the six members of the V alpha 8 subfamily (five functional members and a pseudogene) from C57Bl/6 mice were examined. Consistent with the "accessibility" model, we show that unrearanged V alpha 8 genes are specifically expressed in the thymus of adult mice. Each of the functional genes was transcribed, but at different levels in the thymus. The five V alpha 8 genes were identical through the first 50 nucleotides of the 3' flanking region, and each contained an open reading frame that was contiguous with the V coding region. More interestingly, two of these putative proteins ended in Cys-X-Cys, a motif that is known to undergo isoprenoid modification. This finding and the conservation in the region that extends beyond the heptamer-nonamer region raise the possibility that some unrearranged V genes may encode proteins that have a novel function during early T cell development.