To investigate whether the V delta 2-(D)-J alpha gene configuration, characteristically associated with the major subset of acute lymphoblastic leukemias in humans, might have a physiologic role in T cell ontogeny, we have looked for V delta 2-C alpha transcripts in the thymus and peripheral blood of normal donors. Here we show by PCR analysis that these transcripts are virtually absent in the PBMC, whereas they are present in fetal and postnatal thymus. Interestingly, over 80% of 43 V delta 2-C alpha cDNAs randomly isolated from one postnatal thymus appeared to maintain an open reading frame. This suggests that in the thymus the V delta 2-C alpha products might be exposed to selective pressure. Furthermore, in two of three thymuses tested for J alpha usage, it was found overrepresented in a J alpha element (J alpha 58) located 2 kb downstream to a pseudo-J (J alpha 61), known to be a hot spot of recombination in alpha beta committed cells. A possible alternative pathway to alpha beta T cell differentiation via a V delta 2-J alpha intermediate is discussed.
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