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

Darcy B. Wilson, Clemencia Pinilla, Dianne H. Wilson, Kim Schroder, César Boggiano, Valeria Judkowski, Jonathan Kaye, Bernhard Hemmer, Roland Martin, Richard A. Houghten

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Recent studies have demonstrated the utility of synthetic combinatorial libraries for the rapid identification of peptide ligands that stimulate clonotypic populations of T cells. Here we screen a decapeptide combinatorial library arranged in a positional scanning format with two different clonotypic 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 specificity of TCR/peptide/MHC interactions. We also demonstrate that many of these deduced ligands are not only effective immunogens in vivo, but are capable of inducing T cell responses to the original native ligands used to generate the clones. These results have significant implications for considerations of T cell specificity and the design of peptide vaccines for infectious disease and cancer using clinically relevant T cell clones of unknown specificity.

Original languageEnglish (US)
Pages (from-to)6424-6434
Number of pages11
JournalJournal of Immunology
Volume163
Issue number12
StatePublished - 1999
Externally publishedYes

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