| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
*
Molecular Statistics and Bioinformatics Section, Biometric Research Branch, National Cancer Institute, and
Neuroimmunology Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD 20892;
Torrey Pines Institute for Molecular Studies and Mixture Sciences, San Diego, CA 92121; and
Clinical Neuroimmunology Group, Department of Neurology, Philipps-University Marburg, Marburg, Germany
The interaction of TCRs with MHC peptide ligands can be highly flexible, so that many different peptides are recognized by the same TCR in the context of a single restriction element. We provide a quantitative description of such interactions, which allows the identification of T cell epitopes and molecular mimics. The response of T cell clones to positional scanning synthetic combinatorial libraries is analyzed with a mathematical approach that is based on a model of independent contribution of individual amino acids to peptide Ag recognition. This biometric analysis compares the information derived from these libraries composed of trillions of decapeptides with all the millions of decapeptides contained in a protein database to rank and predict the most stimulatory peptides for a given T cell clone. We demonstrate the predictive power of the novel strategy and show that, together with gene expression profiling by cDNA microarrays, it leads to the identification of novel candidate autoantigens in the inflammatory autoimmune disease, multiple sclerosis.
This article has been cited by other articles:
|
|
 |
|
  S. Markovic-Plese Degenerate T-Cell Receptor Recognition, Autoreactive Cells, and the Autoimmune Response in Multiple Sclerosis Neuroscientist, June 1, 2009; 15(3): 225 - 231. [Abstract] [PDF]
|
|
|
|
 |
|
 V. Voelter, N. Rufer, S. Reynard, G. Greub, R. Brookes, P. Guillaume, F. Grosjean, T. Fagerberg, O. Michelin, S. Rowland-Jones, et al. Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor Int. Immunol., August 1, 2008; 20(8): 1087 - 1096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Lunemann, H. Gelderblom, M. Sospedra, J. A. Quandt, C. Pinilla, A. Marques, and R. Martin Cerebrospinal Fluid-Infiltrating CD4+ T Cells Recognize Borrelia burgdorferi Lysine-Enriched Protein Domains and Central Nervous System Autoantigens in Early Lyme Encephalitis Infect. Immun., January 1, 2007; 75(1): 243 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lustgarten, A. L. Dominguez, and C. Pinilla Identification of Cross-Reactive Peptides Using Combinatorial Libraries Circumvents Tolerance against Her-2/neu-Immunodominant Epitope J. Immunol., February 1, 2006; 176(3): 1796 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sospedra, P. A. Muraro, I. Stefanova, Y. Zhao, K. Chung, Y. Li, M. Giulianotti, R. Simon, R. Mariuzza, C. Pinilla, et al. Redundancy in Antigen-Presenting Function of the HLA-DR and -DQ Molecules in the Multiple Sclerosis-Associated HLA-DR2 Haplotype J. Immunol., February 1, 2006; 176(3): 1951 - 1961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Judkowski, G. M. Allicotti, N. Sarvetnick, and C. Pinilla Peptides From Common Viral and Bacterial Pathogens Can Efficiently Activate Diabetogenic T-Cells Diabetes, September 1, 2004; 53(9): 2301 - 2309. [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]
|
|
|
|
|
|
V. Rubio-Godoy, V. Dutoit, Y. Zhao, R. Simon, P. Guillaume, R. Houghten, P. Romero, J.-C. Cerottini, C. Pinilla, and D. Valmori Positional Scanning-Synthetic Peptide Library-Based Analysis of Self- and Pathogen-Derived Peptide Cross-Reactivity with Tumor-Reactive Melan-A-Specific CTL J. Immunol., November 15, 2002; 169(10): 5696 - 5707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Dutoit, V. Rubio-Godoy, M. J. Pittet, A. Zippelius, P.-Y. Dietrich, F. A. Legal, P. Guillaume, P. Romero, J.-C. Cerottini, R. A. Houghten, et al. Degeneracy of Antigen Recognition as the Molecular Basis for the High Frequency of Naive A2/Melan-A Peptide Multimer+ CD8+ T Cells in Humans J. Exp. Med., July 15, 2002; 196(2): 207 - 216. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
