T-cell receptor δ-chain diversity in peripheral lymphocytes

A small percentage (≃5%) of the cells in the adult thymus expresses a heterodimetric receptor, γδ, that exhibits extensive clonal diversity. The specificity and function of these cells are unclear. Furthermore, it is not known if their role in the immune system is primarily one that operates within the thymus during the selection of the T-cell repertoire or if they function primarily in an antigen-recognition capacity in the peripheral lymphoid system. To examine if γδ⁺ T cells in the periphery are as diverse as those in the thymus, we used the polymerase chain reaction to amplify δ-chain transcripts from polyclonal populations of thymic and splenic lymphocytes (the latter were derived from allogeneic mixed lymphocyte cultures). The nucleotide sequences of δ chains from the spleen, like those from the thymus, were all different. Most of the diversity was present in the region between the variable (V) and joining (J) gene segments and was generated through the use of the two known diversity (D) elements, Dδ1 and D(δ2), and by the addition or deletion of bases at the V(δ)D(δ1), D(d1)D(δ2), and D(δ2)J(δ) junctions. The extensive γδ repertoire among peripheral cells suggests that they have the potential to recognize an array of ligands that could be as diverse as those recognized by αβ⁺ cells. The amplification strategy described here can be used to analyze rapidly the diversity exhibited by any of the members of the immunoglobulin-like gene families that undergo rearrangement.