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

Portal venous (p.v.) immunization with multiple minor histoincompatible cel ls leads to antigen-specific increased skin allograft survival. gamma delta TCR+ hybridoma cells, prepared from mesenteric lymphocytes of p.v. immuniz ed animals, can adoptively transfer this increased graft survival to naive animals. We have analyzed V gamma V delta gene usage, and TCR gamma-chain j unctional diversity in gamma delta TCR+ 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 hyb ridoma cells were derived, one expressing a common gamma-chain junctional s equence which was also found in > 85% of the hybridomas derived following i .v. immunization, while the other set showed remarkable gamma-chain junctio nal sequence diversity. The diversity seen in these latter hybridomas was a ssociated with the antigen specificity of the hybridoma cells. Cells expres sing these 'unique' TCR junctional sequences were stimulated to produce cyt okines both by hsp and by minor-histocompatibility-specific irradiated peri toneal cells. Cells expressing TCR with a common gamma-chain junctional seq uence were stimulated to cytokine production by MHC-matched but minor-histo compatibility mismatched (as well as matched) peritoneal cells, but not by hsp. We suggest that p.v. immunization results ill stimulation of both anti gen-specific and non-specific regulatory gamma delta TCR+ cells, which can be distinguished by gamma-chain TCR sequence diversity. (C) 1998 Elsevier S cience B.V. All rights reserved.