T Cell Receptor δ Gene Rearrangement and T Early α (TEA) Expression in Immature αβ LineageThymocytes: Implications for αβ/γδ Lineage Commitment

Abstract

Mature T cells comprise two mutually exclusive lineages expressing heterodimeric αβ or γδ antigen receptors. During development, β, γ, and δ genes rearrange before α, and mature γδ cells arise in the thymus prior to αβ cells. The mechanism underlying commitment of immature T cells to the αβ or γδ lineage is controversial. Since the δ locus is located within the α locus, rearrangement of α genes leads to deletion of δ. We have examined the rearrangement status of the δ locus immediately prior to α rearrangement. We find that many thymic precursors of αβ cells undergo VDJδ rearrangements. Furthermore, the same cells frequently coexpress sterile T early α (TEA) transcripts originating 3′ of Cδ and 5′ of the most upstream Jα, thus implying that individual αβ lineage cells undergo sequential VDJδ and VJα rearrangements. Finally, VDJδ rearrangements in immature αβ cells appear to be random, supporting models in which αβ lineage commitment is determined independently of the rearrangement status at the TCR δ locus.