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

Summary Clonal T‐cell anergy has been proposed as a mechanism to ensure peripheral tolerance in vivo. Anergy has been reported to result from T cell activation with inappropriate antigen‐presenting cells (APC) or, in the case of CD4+ T cells, also by altered peptide ligands. This study reveals that altered hapten ligands can also induce anergy in CD8+ T cells. The Kb‐restricted, trinitrophenyl (TNP) specific cytotoxic T lymphocyte (CTL) clone E6 was found to lyse target cells presenting the TNP‐modified peptides M4L‐TNP (derived 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 inhibited M4L‐TNP‐mediated kill if expressed on the same target cell. Moreover, when presented alone on APC, O4DNP, but not M4L‐DNP, induced anergy in clone E6 by preventing its subsequent proliferative response to M4L‐TNP. The anergic state did not affect agonist‐specific cytolysis or T‐cell receptor (TCR) down‐modulation by the anergized CTL, and proliferative responses were regained upon addition of interleukin (IL)‐2 or IL‐12 plus IL‐18. These findings 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 also in contact hypersensitivity reactions to haptens.