Specificity of human T lymphocytes expressing a gamma/delta T cell antigen receptor. Recognition of a polymorphic determinant of HLA class I molecules by a gamma/delta clone.
Alloreactive clones expressing T cell receptor (TcR) gamma/delta were derived by limiting dilution from CD3+ CD4- CD8- WT31- populations stimulated in allogeneic mixed lymphocyte culture. These clones specifically lysed phytohemagglutinin-induced blast cells bearing the stimulating alloantigens, whereas they had no effect on autologous or allogeneic unrelated target cells. Analysis of the reactivity with monoclonal antibodies (mAb) specific for two different subsets of TcR gamma/delta (BB3 and delta-TCS-1) showed that five out of nine clones were BB3+, whereas the remaining reacted with delta-TCS-1. Therefore, we can conclude that both subsets of TcR gamma/delta+ cells are able to specifically recognize and lyse allogeneic cells. mAb directed against the CD3-TcR gamma/delta molecular complex strongly inhibited the specific cytolytic activity of TcR gamma/delta+ clones, whereas they had no effect on the lysis of the natural killer-sensitive K-562 target cells mediated by the same clones. An alloreactive delta-TCS-1+ clone (LM12) was further characterized for its specificity. LM12 clone had been derived after stimulation in mixed lymphocyte culture against donor M.M. (HLA typing: Aw68, 24; B35, w55; DR1, 7). The analysis of a large panel of phytohemagglutinin-induced target cells revealed that only the HLA-A24+ target cells were lysed. The direct evidence that the A24 molecule represented the restriction element was provided by experiments using A24-transfected murine P815 target cells. Thus, clone LM12 efficiently lysed A24-transfected P815 cells, but not the same cells untransfected or transfected with the Cw3 gene. Therefore, it appears that polymorphic determinants of class I major histocompatibility complex molecules can be the target of TcR gamma/delta+ alloreactive cell recognition.
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Instituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
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Malnati
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Battista Ferrara
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Barocci
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D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D002469:Cell Separation; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D011110:Polymorphism, Genetic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta