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

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Abstract
Monoclonal antibodies (mAb) reactive against the γ/δ T cell antigen receptor (TcR) have been used to characterize the distribution and structural properties of γ/δ TcR-bearing lymphocytes in blood and thymus. Consistent with prior reports the TcR γ/δ-1 and δ-1 mAb react with all γ/δ TcR+ T lymphocytes in blood and thymus. By contrast the TCS-δ mAb was found only to react with a subset of the γ/δ TcR-bearing T cell population. Several lines of evidence suggest that this reagent preferentially reacts with the Vδ1 gene product. Using these reagents, it was observed that γ/δ 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-δ (possibly Vδ1)-bearing cells comprised less than 30% of the total γ/δ-TcR+ population. Biochemical analysis demonstrated that the predominant form of the γ/δ TcR in adult peripheral blood is a disulfide-linked heterodimer, indicating preferential use of the C,1 gene. The δ TcR chain from these TcR-γ/δ-1+/TCS-δ− 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 γ/δ TcR+ thymocytes were predominantly TcR-γ/δ-l+/TCS-δ+, and preferentially expressed Vδl. Moreover, both disulfide-bonded and nondisulfide-bonded γ/δ TcR heterodimers were expressed in all thymuses examined and both forms were contained within the TCS-δ+ thymic subset. Similar to recent findings in the mouse, these studies suggest a possible bias in the structural form of γ/δ TcR based on tissue location.