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

Abstract

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.

Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis.

“…It is noteworthy that ally/b clones that had been derived with autologous LCL and PBL stimulators, and thus were never exposed to allogeneic determinants in vitro, still mediated the typical pattern of cytolysis. These results support the idea that our y/b clones probably do not recognize polymorphic or nonpolymorphic MHC molecules as suggested for other y/b cells (26,28,(33)(34)(35) . It is conceivable that our y/b cells could recognize relatively nonpolymorphic determinants that are expressed in sufficient quantities on only a minority of target cells.…”

Peripheral selection of V delta 1+ cells with restricted T cell receptor delta gene junctional repertoire in the peripheral blood of healthy donors.

“…The nature of presenting molecules that may be potentially involved in antigen recognition is unclear, at least for the majority of"//is T cells, although evidence for allorecognition of MHC class I (15) and II (16), and of other less polymorphic molecules (17)(18)(19) has been documented. A few examples of clones recognizing nominal antigens in the context of MHC molecules have also been described (20,21).…”

γδ-T cells: an unpolished sword in human anti-infection immunity

“…In addition to TLRs, cd TCRs can induce the anti-infection activity of cd-T cells by recognizing multiple pathogen-derived peptides [80][81][82] and unprocessed pathogen-related proteins such as tetanus toxoid, 83 herpes simplex virus glycoprotein I, 84 mycobacterial purified protein derivatives, 85,86 staphylococcal enterotoxin A, 87 listeriolysin O 88 and some heat shock proteins, 85,89 which undoubtedly improves the efficiency of cd-T cell-mediated immune responses during the very early phases of infections without the need to interact with APCs. Finally, there are still debates regarding whether cd-T cells also possess antigen specificity similar to ab-T cells, although rapid recall expansions of clonotypic cd-T cells have been found in mycobacterial 90 and Listeria monocytogenes 53 infections.…”