Vγ segments are selected based on their proximity to the J segment during the rearrangement of the γδ TCR in fetal stage.

T cell receptor genes are created by stitching together three gene segments—V, D, and J—in different arrangements. But how each set of T cells selects its segments is not clear. Xiong et al. (page 929) now find that, for a set of fetal T cell γδ chains, the appeal of a V segment lies in its location relative to the chosen J segment.

In the fetal stage, γδ T cells prefer to use Vγ3 or Vγ4 gene segments, whereas T cells in the adult thymus instead use Vγ2 or Vγ5. Because Vγ3 and Vγ4 are closer to the J segments, Xiong et al. wondered whether V segment selection is dictated simply by their position. Closer V segments are used preferentially in fetal immunoglobulin genes as well, but in that case, proximity correlated with greater transcription and histone acetylation.

To test their new idea, the group engineered mice in which the γ locus was altered to replace the Vγ3 segment with a Vγ2 segment. The fetal γδ T cells in these mice now included the new Vγ2 segment in preference to the more distant Vγ2 segment. They only included more distant gene segments if closer segments were deleted. How the nearby segments shut out their more remote neighbors is not yet known.

The accessibility of the V segments seemed to be equal across the board in fetal cells, as Xiong et al. found that transcription rates didn't predict which segments were used. But in adult γδ T cells, the unused segments had lower levels of transcription. Perhaps the gene segments used during the fetal stage become inaccessible during adulthood, leaving only more distant choices.