Inhibition of naive class I-restricted T cells by altered peptide ligands

Abstract

Amino acid variants of an antigenic peptide or altered peptide ligands have previously been investigated with CD4+ and CD8+ T cells. However, for CD8+ T cells, only clones (which are continually restimulated in vitro) have been assessed. Using TCR transgenic mice specific for a class I Kb-restricted OVA peptide (OVAp; OT-I mice) as a source of naive CD8+ T cells, single amino acid variants of the OVAp were analysed in vitro for their ability to antagonize the proliferative and cytotoxic function of naive OT-I cells. Peptides with substitutions at TCR contact residues were found to be the most potent antagonists of OT-I cell function. Those peptides that inhibited activation of cells to proli..