CHARACTERIZATION OF TRANSCRIPTS FROM UNREARRANGED V-ALPHA-8 GENES IN THE THYMUS

The genes that encode the alpha- and beta-chains of the TCR undergo pr ogrammed rearrangement during differentiation of a T cell in the thymu s, but it is not known what controls the order and specificity of the rearrangement event. By analogy with Ig genes, it is possible that tra nscription of an unrearranged V region gene may be necessary for ''acc ess'' of the recombinase. To begin to address this issue, the six memb ers of the Valpha8 subfamily (five functional members and a pseudogene ) from C57Bl/6 mice were examined. Consistent with the ''accessibility '' model, we show that unrearranged Valpha8 genes are specifically exp ressed in the thymus of adult mice. Each of the functional genes was t ranscribed, but at different levels in the thymus. The five Valpha8 ge nes 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 pr oteins ended in Cys-X-Cys, a motif that is known to undergo isoprenoid modification. This finding and the conservation in the region that ex tends beyond the heptamer-nonamer region raise the possibility that so me unrearranged V genes may encode proteins that have a novel function during early T cell development.