Clonal anergy induced in a CD8+ hapten-specific cytotoxic T-cell clone by an altered hapten-peptide ligand

Clonal T-cell energy has been proposed as a mechanism to ensure peripheral tolerance in vivo. Anergy has been reported to result from T cell activatio n with inappropriate antigen-presenting cells (APC) or, in the case of CD4( +) T cells. also by altered peptide ligands. This study reveals that altere d hapten ligands can also induce anergy in CD8(+) T cells. The K-b-restrict ed, trinitrophenyl (TNP) specific cytotoxic T lymphocyte (CTL) clone E6 was found to lyse target cells presenting the TNP-modified peptides M4L-TNP (d erived from mouse serum albumin) or O4TNP (derived from chicken ovalbumin), but not the corresponding dinitrophenol (DNP)-modified peptides. However, whereas M4L-DNP was found totally unreactive. O4DNP antagonistically inhibi ted M4L-TNP-mediated kill if expressed on the same target cell, Moreover. w hen presented alone on APC, O4DNP, but not M4L-DNP, induced anergy in clone E6 by preventing its subsequent proliferative response to M4L-TNP. The ane rgic state did not affect agonist-specific cytolysis or T-cell receptor (TC R) down-modulation by the anergized CTL, and proliferative responses were r egained upon addition of interleukin (IL)-2. or IL-12 plus IL-18. These fin dings substantiate the similarity between hapten-and peptide-recognition by T cells. The induction as well as the reversal of anergy in CD8(+) CTL may thus be of relevance not only in autoimmunity or tumour rejection, but als o in contact hypersensitivity reactions to haptens.