Human T cell receptor-γ and -δ chain pairing analyzed by transfection of a T cell receptor-δ negative mutant cell line

Specific TCR V(γ) and V(δ) segments are found to be coordinately used on subpopulations of γδ T lymphocytes. The reasons for this phenomenon are unknown, but may include the inability of particular chains expressing unique V(δ) and V(γ) segments to physically associate. V(δ)2 is typically used together with V(γ)2 on human peripheral blood γδ T lymphocytes. To examine whether V(δ)2 can be used in conjunction with distinct V(γ) segments, a TCR^- mutant of the human γδ T cell line MOLT-13, which expresses parental TCRγ (Vγ1.3) but not TCR-δ protein, was transfected with plasmids containing full-length TCR-δ cDNA using either V(δ)2 or V(δ)3. TCR reconstitution was successful in both transfectants and resulted in TCR protein and RNA levels similar to that of the parental MOLT-13 cell line. These cell lines could be activated through their receptors as assessed by increases in cytoplasmic free calcium. These studies imply that physical constraints cannot explain the observed chain pairing preferences. Other possible explanations are discussed.