Structural and serological heterogeneity of γ/δ T cell antigen receptor expression in thymus and peripherar blood

Monoclonal antibodies (mAb) reactive against the gamma/delta T cell antigen receptor (TcR) have been used to characterize the distribution and structural properties of gamma/delta TcR-bearing lymphocytes in blood and thymus. Consistent with prior reports the TcR gamma/delta-1 and delta-1 mAb react with all gamma/delta TcR+ T lymphocytes in blood and thymus. By contrast the TCS-delta mAb was found only to react with a subset of the gamma/delta TcR-bearing T cell population. Several lines of evidence suggest that this reagent preferentially reacts with the V delta 1 gene product. Using these reagents, it was observed that gamma/delta TcR+ T lymphocytes comprise 4.6 +/- 3.5% (range 1.0-16.3%) of peripheral blood lymphocytes. However, analysis of peripheral blood from normal adult donors revealed that in 29 of 32 the TCS-delta (possibly V delta 1)-bearing cells comprised less than 30% of the total gamma/delta-TcR+ population. Biochemical analysis demonstrated that the predominant form of the gamma/delta TcR in adult peripheral blood is a disulfide-linked heterodimer, indicating preferential use of the C gamma 1 gene. The delta TcR chain from these TcR-gamma/delta-1+/TCS-delta- T cells was remarkably basic in charge, as analyzed by nonequilibrium pH gradient electrophoresis. By contrast with peripheral blood the majority of freshly isolated and interleukin 2-cultured gamma/delta TcR+ thymocytes were predominantly TcR-gamma/delta-1+/TCS-delta +, and preferentially expressed V delta 1. Moreover, both disulfide-bonded and nondisulfide-bonded gamma/delta TcR heterodimers were expressed in all thymuses examined and both forms were contained within the TCS-delta + thymic subset. Similar to recent findings in the mouse, these studies suggest a possible bias in the structural form of gamma/delta TcR based on tissue location.