Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4(+) T cells and induce T cell responses to native peptide ligands

Recent studies have demonstrated the utility of synthetic combinatorial lib raries for the rapid identification of peptide ligands that stimulate clono typic populations of T cells. Here we screen a decapeptide combinatorial li brary arranged in a positional scanning format with two different clonotypi c populations of CD4(+) T cells to identify peptide epitopes that stimulate proliferative responses by these T cells in vitro, An extensive collection of mimic peptide sequences was synthesized and used to explore the fine sp ecificity of TCR/peptide/MHC interactions. We also demonstrate that many of these deduced ligands are not only effective immunogens in vivo, but are c apable of inducing T cell responses to the original native ligands used to generate the clones. These results have significant implications for consid erations of T cell specificity and the design of peptide vaccines for infec tious disease and cancer using clinically relevant T cell clones of unknown specificity.