Non‐random expression of T cell receptor γ and δ variable gene segments in functional T lymphocyte clones from human peripheral blood

Abstract

Human T cell receptor (TcR) γδ displays a variety of protein forms. Disulfide-linked (type 1) or non disulfide-linked (type 2) receptors occur, with γ chains encoded by the C_γ1 or the C_γ2 gene segment, respectively. Exon 2 of C_γ2 may either be duplicated or triplicated (type 2a or 2b receptors). TcR γ chains differ in molecular mass and charge between type 1 and type 2 receptors. The δ chains as well as the γ chains have different structural properties between receptor types. This cannot be due to the use of different C_δ gene segments, since the genome encodes only one. To understand the genetic basis of this dichotomy in γ/δ combinations, rearrangement and expression of V_γ, J_γ, C_γ and V_δ gene segments were determined in TcR γ/δ⁺ clones derived randomly from peripheral blood of normal donors. Most clones used C_γ1, a minority C_γ2. The different protein properties of receptor types could be explained by the nonrandom expression of V_γ(J_γ) and V_δ gene segments. Type 1 receptors preferentially used γ chains encoded by the V_γ9 and J_γ1.2 gene segments together with δ chains encoded by V_δ2. In type 2a receptors, V_γ9 was not predominant; often other V_γ gene segments were employed, but then in high frequency in coordination with V_δ1. Reactivity of the clones with monoclonal antibodies anti-TiγA, BB3 and δ-TCS-1 correlated with the expression of the V_γ9, V_δ2 and V_δ1 gene segments, respectively. Therefore, V_γ and V_δ use in TcR γ/δ⁺ cells from peripheral blood of eight healthy individuals, including the two donors of the clones, could be determined tentatively by double immunofluorescence. Indeed, the V_γ9-V_δ2 combination was predominant, while the V_γ9-V_δ1 and particularly the V_γ9-“V_δother” combination was rare. These data indicate that the TcR γδ repertoire in peripheral blood of normal individuals is largely dependent on junctional diversity and suggest that selection of receptors occurs.