The adult T-cell receptor 5-chain is diverse and distinct from that of fetal thymocytes

Abstract

T lymphocytes recognize foreign molecules using the T-cell receptor (TCR), a disulphide-linked heterodimer closely associated with the CD3 polypeptide complex on the cell surface. The TCR ^αβ heterodimers seem largely responsible for the recognition properties of both helper (T_H) and cytotoxic (T_c) T cells^1,2. Recently, a second CDS-associated T-cell receptor heterodimer, γδ, has been described^3–9. Cells bearing the γδ receptor appear before those bearing αβ during thymic ontogeny^8,9 and persist as a minor component (1–10%) of mature peripheral T cells. Their function is unknown. As there are a limited number of functional TCR V_γ gene segments¹⁰, the size and potential diversity of the V_δ repertoire is important for the number of different antigens that may be recognized by γδ heterodimers. The δ-chain locus is located 75 kilobases (kb) 5′ to the TCR C_α coding region^11,12, raising the possibility that the α and δ V-region repertoires may overlap. Also, analysis of rearrangements at the δ-chain locus in developing thymocytes shows distinct fetal and adult patterns¹¹ indicating that there may be differences between the fetal and adult V_delta; repertoires. To address these questions, we have characterized a large number of δ-containing complementary DNA clones from adult double-negative thymocytes (CD4^–8^–), an immature population that is enriched for γδ-bearing cells⁵. We find that a limited number of V_δ sequences are used, showing little overlap with known adult V_αs and differing significantly from fetal V_δs But as two D elements may participate simultaneously in V_δ gene assembly, and random nucleotides may be added at any one of three junctional points, the potential number of different δ chains that can be made in the adult thymus is very large (∼10¹³).