title: Combinatorial peptide library-based identification of peptide ligands for tumor-reactive cytolytic T lymphocytes of unknown specificity.
abstract: A novel approach for the identification of tumor antigen-derived sequences recognized by CD8(+) cytolytic T lymphocytes (CTL) consists in using synthetic combinatorial peptide libraries. Here we have screened a library composed of 3.1 x 10(11) nonapeptides arranged in a positional scanning format, in a cytotoxicity assay, to search the antigen recognized by melanoma-reactive CTL of unknown specificity. The results of this analysis enabled the identification of several optimal peptide ligands, as most of the individual nonapeptides deduced from the primary screening were efficiently recognized by the CTL. The results of the library screening were also analyzed with a mathematical approach based on a model of independent and additive contribution of individual amino acids to antigen recognition. This biometrical data analysis enabled the retrieval, in public databases, of the native antigenic peptide SSX-2(41-49), whose sequence is highly homologous to the ones deduced from the library screening, among the ones with the highest stimulatory score. These results underline the high predictive value of positional scanning synthetic combinatorial peptide library analysis and encourage its use for the identification of CTL ligands.
authors.affiliation: Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Rubio-Godoy
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.forename: Valerie
authors.initials: V
authors.lastname: Dutoit
authors.forename: Catherine
authors.initials: C
authors.lastname: Servis
authors.forename: Amy
authors.initials: A
authors.lastname: Schink
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
authors.forename: Yindong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Richard A
authors.initials: RA
authors.lastname: Houghten
authors.forename: Clemencia
authors.initials: C
authors.lastname: Pinilla
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D008024:Ligands; D019151:Peptide Library; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D008024:Ligands; D019151:Peptide Library