Coordinated Vγ and Vδ gene segment rearrangements in human T cell receptor γ/δ+ lymphocytes

Abstract

Monoclonal antibodies (mAb) were used to characterize a panel (n = 46) of T cell receptor (TcR) γ/δ⁺ T cell clones. Three of these antibodies have been described to react with specific variable region‐encoded protein products and can therefore be used to detect functional gene rearrangements. The majority of peripheral blood‐derived clones (43 out of 45) expressed the epitopes recognized by mAb BB3, encoded by the V_δ2 gene segment and mAb TiγA, encoded by the V_γ9 gene segment. These clones lacked the antigenic determinant recognized by mAb δ‐TCS‐1, encoded by the V_δ1 gene segment. The other two peripheral blood‐derived clones and an ascites‐derived clone were TiγA^‐, BB3^‐ and δ‐TCS‐1⁺. Biochemical analysis revealed that all TiγA⁺, BB3⁺ T cell clones expressed the disulfide‐linked form of the receptor. The two peripheral blood‐derived δ‐TCS‐1⁺ T cell clones expressed the nondisulfide‐linked form whereas the ascites‐derived δ‐TCS‐1⁺ clone, AK119 expressed the disulfide‐linked form of the TcRγ/δ heterodimer. This indicates that V_δ1‐encoded δ chains can be associated either with a C_γ1‐ or a C_γ2‐encoded γ chain. The preferential use of certain V_γ and V_δ gene segments suggests the existence of a limited combinatorial diversity in TcRγ/δ heterodimers, i.e. TiγA⁺ (V_γ9), BB3⁺ (V_δ2) and δ‐TCS‐1^‐ disulfide‐linked heterodimers and TiγA^‐, BB3^‐ and δ‐TCS‐1⁺ (V_δ1) disulfide‐ or non disulfide‐linked forms.