Human TCR-gamma+/delta+, CD8+ T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion

doi:10.1084/jem.169.5.1847

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Human TCR-gamma+/delta+, CD8+ T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion

D Kozbor, G Trinchieri, DS Monos, M Isobe, G Russo, JA Haney, C Zmijewski and CM Croce
Wistar Institute, Philadelphia, Pennsylvania 19104.

We have analyzed the ability of human gamma+/delta+ T cells to recognize a nominal antigen in association with MHC molecules. A TT- specific T cell line with approximately 40% gamma+/delta+ T cells was established from a hyperimmunized donor, D.F., by stimulation with antigen and autologous APC. Three DF-derived gamma+/delta+ clones were CD8+ as determined by immunofluorescence staining, and by Southern and Northern blotting with probes detecting delta chain rearrangement and delta and gamma chain transcripts, respectively. The gamma+/delta+ clones responded to stimulation with TT, but not TNP-BSA, and autologous APC by proliferation and IFN-gamma production. No proliferation or IFN-gamma production was detected when TT-specific T cell clones were stimulated with either TT or autologous APC only. The response to TT was enhanced by addition of exogenous IL-2. The use of allogeneic APC from 19 donors sharing one HLA-determinant with the autologous donor D.F., showed that the gamma+/delta+ T cells responded to TT with HLA-DR4-related restriction as measured by proliferation and IFN-gamma production. These results demonstrate that gamma/delta receptors can recognize non-MHC-encoded foreign antigen in a self-MHC- restricted fashion.
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