TCR diversity in gammadeltaTCR+ hybridomas derived from mice given portal vein donor-specific pre-immunization and skin allografts.

Portal venous (p.v.) immunization with multiple minor histoincompatible cells leads to antigen-specific increased skin allograft survival. GammadeltaTCR+ hybridoma cells, prepared from mesenteric lymphocytes of p.v. immunized animals, can adoptively transfer this increased graft survival to naive animals. We have analyzed VgammaVdelta gene usage, and TCR gamma-chain junctional diversity in gammadeltaTCR+ hybridomas from mice immunized with different antigen combinations by p.v. or conventional lateral tail vein (i.v.) immunization. Following p.v. immunization two independent sets of hybridoma cells were derived, one expressing a common gamma-chain junctional sequence which was also found in > 85% of the hybridomas derived following i.v. immunization, while the other set showed remarkable gamma-chain junctional sequence diversity. The diversity seen in these latter hybridomas was associated with the antigen specificity of the hybridoma cells. Cells expressing these 'unique' TCR junctional sequences were stimulated to produce cytokines both by hsp and by minor-histocompatibility-specific irradiated peritoneal cells. Cells expressing TCR with a common gamma-chain junctional sequence were stimulated to cytokine production by MHC-matched but minor-histocompatibility mismatched (as well as matched) peritoneal cells, but not by hsp. We suggest that p.v. immunization results in stimulation of both antigen-specific and non-specific regulatory gammadeltaTCR+ cells, which can be distinguished by gamma-chain TCR sequence diversity.