Separate lineages of T cells expressing the αβ and γδ receptors

Abstract

THE T-cell antigen receptor is a heterodimer molecule composed of either αβ or γδ chains. The αβ receptor molecules are expressed mainly in CD4⁺ CD8⁻ and CD4⁻CD8⁺ T cells (helper and killer T cells respectively), whereas the γδ receptor molecules are expressed mainly in CD4⁻CD8^- T cells^1–3. CD4⁺CD8⁻ and CD4⁻CD8⁺ T cells arise from a class of CD4⁻CD8⁻ T cells during thymus development⁴, raising the question of whether cells rearranging their γδ receptors later give rise to αβ T cells by further rearrangements of their receptor genes, or whether rearrangements and expression of the receptor genes occur in separate lineages. The δ -chain gene is located between the Vα (variable) and Jα(joining) gene segments^5,6 and when the rearrangements allowing α- and β-receptors occur, the DNA between these segments is deleted as small circles which can be isolated from developing thymocytes^7,8. The rearrangement status of the δ -chain gene in the α-circles can therefore be investigated to see whether α-chain and δ -chain expression occur in parallel lineages or sequentially within a lineage. We find that the δ -chain gene in the T-cell receptor α-circles has a germline configuration, indicating that αβ and γδ T cells are distinct lineages.