Selective activation of CD8 T cell effector functions by epitope variants of lymphocytic choriomeningitis virus glycoprotein

Abstract

We provide evidence for selective activation of different effector functions of CD8+ T lymphocytes by altered peptide ligands. A T cell epitope from the glycoprotein of lymphocytic choriomeningitis virus (p33-41) and single amino acid variants thereof were used for primary in vitro induction of CTL clones. When the CTL were analyzed for cytotoxicity, proliferation, IFN-gamma production, and Ca2+ mobilization, we found that some of the clones showed activation of only their cytotoxic effector function when stimulated with variants of their inducing peptides. For one clone, cytotoxic reactivity was readily detected to the inducing peptide and three of four variants, but only the former was also able to trigger proliferation, IFN-gamma production, and Ca2+ mobilization. Another clone also revealed this dichotomy, but in this case some of the altered peptide ligands in addition to the inducing peptide were able to stimulate the full spectrum of effector functions, whereas others only stimulated cytotoxicity. A third clone revealed inefficient triggering of some effector functions by the peptide variants. Our data suggest that, as described for CD4 T cells, altered peptide ligands may lead to partial activation of effector functions of CD8 T cells. In addition, ligands with glycine substitutions in potential TCR contact positions induced CTL, which were able to recognize peptides with a variety of amino acids in the former glycine position.