Expression and function of gamma delta- and alpha beta-T cell receptor heterodimers on human somatic T cell hybrids.

Abstract

T cell somatic hybrids were obtained by fusion of human tetanus toxoid-specific gamma + delta + T cells and a T cell lymphoma cell line that expresses beta-chain but not alpha-chain transcripts. The hybrids simultaneously and independently expressed alpha beta and gamma delta TCR heterodimers on the cell surface without any significant differences in the level of expression. No heterodimers containing alpha delta-, beta delta-, beta gamma-, and alpha gamma-chains were transported to the cell membrane, indicating a chain specificity in dimer formation. The presence of productively rearranged gamma- and delta-alleles in the hybrid cells and immunoprecipitation of an identical type of TCR-gamma delta from both hybrid and parental gamma + delta + T cells suggests that TCR-gamma delta on the hybrid cells derives from gamma + delta + T cells. Anti-TCR (TCS-delta 1 or WT31) and anti-CD3 antibodies induced a rapid increase in [Ca2+]i in the double-positive hybrids and their variants positive for either the alpha beta or gamma delta complex. Double positive hybrid cells were refractory to stimulation with anti-CD3 antibody after pretreatment with a mixture of anti-TCR-gamma delta and anti-TCR-alpha beta antibodies but not with either antibody alone indicating the functional independence of the two receptors. However, only gamma delta heterodimer receptor was able to respond to tetanus toxoid presented on autologous APC as measured by induction of the p55 chain of IL-2R on stimulated cells.