title: Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4+ T cells and induce T cell responses to native peptide ligands.
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.
authors.affiliation: Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA. dbwilson@tpims.org
authors.forename: D B
authors.initials: DB
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Pinilla
authors.forename: D H
authors.initials: DH
authors.lastname: Wilson
authors.forename: K
authors.initials: K
authors.lastname: Schroder
authors.forename: C
authors.initials: C
authors.lastname: Boggiano
authors.forename: V
authors.initials: V
authors.lastname: Judkowski
authors.forename: J
authors.initials: J
authors.lastname: Kaye
authors.forename: B
authors.initials: B
authors.lastname: Hemmer
authors.forename: R
authors.initials: R
authors.lastname: Martin
authors.forename: R A
authors.initials: RA
authors.lastname: Houghten
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry / Q000276:immunology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D019151:Peptide Library; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D003574:Cytochrome c Group; D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D004676:Myelin Basic Protein; D019151:Peptide Library; D010455:Peptides