Y8 T Lymphocytes

TCR ap- and yS-expressing thymocytes are separate lineages with a common precursor. In fetal thymuses, the first TCR gene rearrangements involve the y and 8 loci. Recombination of TCR y and 8 loci proceeds in a fashion similar to that of other antigen receptor gene rearrangements, although the order of rearrangement appears to be less rigid than in other loci. In a developing doublenegative T cell, rearrangement of TCR p, y, or 8 loci is initially possible. If a cell succeeds in productively rearranging its TCR y as well as its TCR 8 loci before it makes a productive TCR p rearrangement, it is selected into the y8 T cell lineage. This happens in about 10% of developing double-negative T cells. About 90% of the time, a productive TCR p gene rearrangement is made first. In this situation, pre-TCR signaling selects these cells to mature into the ap T cell lineage, and eventual deletion of TCR 8 when TCR a is rearranged (the TCR 8 locus is embedded in the TCR a locus) results in irreversible commitment to the ap lineage.

The diversity of the y8 T cell repertoire is theoretically even greater than that of the ap T cell repertoire, in part because the heptamer-nonamer recognition sequences adjacent to D segments permit D-to-D joining. Paradoxically, however, the actual diversity of expressed y8 TCRs is limited because only a few of the available V, D, and J segments are used in mature y8 T cells, for unknown reasons. This limited diversity is reminiscent of the limited diversity of the B-1 subset of B lymphocytes and is in keeping with the concept that y8 T cells serve as an early defense against a limited number of commonly encountered microbes at epithelial barriers.

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