HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wilson, D. B. Articles by Houghten, R. A. Search for Related Content PubMed PubMed Citation Articles by Wilson, D. B. Articles by Houghten, R. A.

Immunogenicity. I. Use of Peptide Libraries to Identify Epitopes That Activate Clonotypic CD4⁺ T Cells and Induce T Cell Responses to Native Peptide Ligands¹

Darcy B. Wilson^2,*, Clemencia Pinilla^*, Dianne H. Wilson^*, Kim Schroder^*, César Boggiano^*, Valeria Judkowski^*, Jonathan Kaye, Bernhard Hemmer^3,, Roland Martin and Richard A. Houghten^*

^* Torrey Pines Institute for Molecular Studies, San Diego, CA 92121; Scripps Research Institute, La Jolla, CA 92037; and National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892

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.

This article has been cited by other articles:

				P. Mana, M. Goodyear, C. Bernard, R. Tomioka, M. Freire-Garabal, and D. Linares Tolerance induction by molecular mimicry: prevention and suppression of experimental autoimmune encephalomyelitis with the milk protein butyrophilin Int. Immunol., March 1, 2004; 16(3): 489 - 499. [Abstract] [Full Text] [PDF]

				A. W. Purcell and J. J. Gorman Immunoproteomics: Mass Spectrometry-based Methods to Study the Targets of the Immune Response Mol. Cell. Proteomics, March 1, 2004; 3(3): 193 - 208. [Abstract] [Full Text] [PDF]

				Y. Uemura, S. Senju, K. Maenaka, L. K. Iwai, S. Fujii, H. Tabata, H. Tsukamoto, S. Hirata, Y.-Z. Chen, and Y. Nishimura Systematic Analysis of the Combinatorial Nature of Epitopes Recognized by TCR Leads to Identification of Mimicry Epitopes for Glutamic Acid Decarboxylase 65-Specific TCRs J. Immunol., January 15, 2003; 170(2): 947 - 960. [Abstract] [Full Text] [PDF]

				C. A. Lawendowski, G. M. Giurleo, Y. Y. Huang, G. J. Franklin, J. M. Kaplan, B. L. Roberts, and C. A. Nicolette Solid-Phase Epitope Recovery: A High Throughput Method for Antigen Identification and Epitope Optimization J. Immunol., September 1, 2002; 169(5): 2414 - 2421. [Abstract] [Full Text] [PDF]

				J. A. M. Borghans and R. J. De Boer Memorizing innate instructions requires a sufficiently specific adaptive immune system Int. Immunol., May 1, 2002; 14(5): 525 - 532. [Abstract] [Full Text] [PDF]

				V. Rubio-Godoy, C. Pinilla, V. Dutoit, E. Borras, R. Simon, Y. Zhao, J.-C. Cerottini, P. Romero, R. Houghten, and D. Valmori Toward Synthetic Combinatorial Peptide Libraries in Positional Scanning Format (PS-SCL)-based Identification of CD8+ Tumor-reactive T-Cell Ligands: A Comparative Analysis of PS-SCL Recognition by a Single Tumor-reactive CD8+ Cytolytic T-Lymphocyte Clone Cancer Res., April 1, 2002; 62(7): 2058 - 2063. [Abstract] [Full Text] [PDF]

				Y. Zhao, B. Gran23, C. Pinilla, S. Markovic-Plese, B. Hemmer, A. Tzou, L. W. Whitney, W. E. Biddison, R. Martin, and R. Simon Combinatorial Peptide Libraries and Biometric Score Matrices Permit the Quantitative Analysis of Specific and Degenerate Interactions Between Clonotypic TCR and MHC Peptide Ligands J. Immunol., August 15, 2001; 167(4): 2130 - 2141. [Abstract] [Full Text] [PDF]

				A. Amrani, P. Serra, J. Yamanouchi, J. D. Trudeau, R. Tan, J. F. Elliott, and P. Santamaria Expansion of the Antigenic Repertoire of a Single T Cell Receptor upon T Cell Activation J. Immunol., July 15, 2001; 167(2): 655 - 666. [Abstract] [Full Text] [PDF]

				C. Trollmo, A. L. Meyer, A. C. Steere, D. A. Hafler, and B. T. Huber Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1{{alpha}}L Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells J. Immunol., April 15, 2001; 166(8): 5286 - 5291. [Abstract] [Full Text] [PDF]

				C. L. Rosa, R. Krishnan, S. Markel, J. P. Schneck, R. Houghten, C. Pinilla, and D. J. Diamond Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries Blood, March 15, 2001; 97(6): 1776 - 1786. [Abstract] [Full Text] [PDF]

				V. Judkowski, C. Pinilla, K. Schroder, L. Tucker, N. Sarvetnick, and D. B. Wilson Identification of MHC Class II-Restricted Peptide Ligands, Including a Glutamic Acid Decarboxylase 65 Sequence, that Stimulate Diabetogenic T Cells from Transgenic BDC2.5 Nonobese Diabetic Mice J. Immunol., January 15, 2001; 166(2): 908 - 917. [Abstract] [Full Text] [PDF]

				B. Hemmer, C. Pinilla, B. Gran, M. Vergelli, N. Ling, P. Conlon, H. F. McFarland, R. Houghten, and R. Martin Contribution of Individual Amino Acids Within MHC Molecule or Antigenic Peptide to TCR Ligand Potency J. Immunol., January 15, 2000; 164(2): 861 - 871. [Abstract] [Full Text] [PDF]