Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zippelius, A. Articles by Romero, P. Search for Related Content PubMed PubMed Citation Articles by Zippelius, A. Articles by Romero, P. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Social Bookmarking                      What's this?

¹ Division of Clinical Onco-Immunology, University Hospital (CHUV), 1011 Lausanne, Switzerland
² Division of Immunology and Allergy, University Hospital (CHUV), 1011 Lausanne, Switzerland
³ Multidisciplinary Oncology Center, University Hospital (CHUV), 1011 Lausanne, Switzerland
⁴ NCCR Molecular Oncology, Swiss Institute for Experimental Cancer Research, 1066 Epalinges, Switzerland
⁵ Department of Clinical Chemistry, Microbiology and Immunology, University Hospital, 9000 Ghent, Belgium
⁶ Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland

Address correspondence to Pedro Romero, Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Hôpital Orthopédique, Niveau 5, Aile Est, Avenue Pierre Decker 4, 1005 Lausanne, Switzerland. Phone: 41-21-3140-176; Fax: 41-21-3147-477; E-mail: pedro.romero{at}isrec.unil.ch

The low frequency of self-peptide–specific T cells in the human preimmune repertoire has so far precluded their direct evaluation. Here, we report an unexpected high frequency of T cells specific for the self-antigen Melan-A/MART-1 in CD8 single–positive thymocytes from human histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained in the peripheral blood of newborns and adults. Postthymic replicative history of Melan-A/MART-1–specific CD8 T cells was independently assessed by quantifying T cell receptor excision circles and telomere length ex vivo. We provide direct evidence that the large T cell pool specific for the self-antigen Melan-A/MART-1 is mostly generated by thymic output of a high number of precursors. This represents the only known naive self-peptide–specific T cell repertoire directly accessible in humans.

Key Words: TREC • Telomere • Melan-A/MART-1 • naive • CD8

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Voelter, V., Rufer, N., Reynard, S., Greub, G., Brookes, R., Guillaume, P., Grosjean, F., Fagerberg, T., Michelin, O., Rowland-Jones, S., Pinilla, C., Leyvraz, S., Romero, P., Appay, V. (2008). Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor. Int Immunol 20: 1087-1096 [Abstract] [Full Text]  
• Derre, L., Ferber, M., Touvrey, C., Devevre, E., Zoete, V., Leimgruber, A., Romero, P., Michielin, O., Levy, F., Speiser, D. E. (2007). A Novel Population of Human Melanoma-Specific CD8 T Cells Recognizes Melan-AMART-1 Immunodominant Nonapeptide but Not the Corresponding Decapeptide. J. Immunol. 179: 7635-7645 [Abstract] [Full Text]  
• Michalek, J., Kocak, I., Fait, V., Zaloudik, J., Hajek, R. (2007). Detection and Long-Term In Vivo Monitoring of Individual Tumor-Specific T Cell Clones in Patients with Metastatic Melanoma. J. Immunol. 178: 6789-6795 [Abstract] [Full Text]  
• Romero, P., Zippelius, A., Kurth, I., Pittet, M. J., Touvrey, C., Iancu, E. M., Corthesy, P., Devevre, E., Speiser, D. E., Rufer, N. (2007). Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes. J. Immunol. 178: 4112-4119 [Abstract] [Full Text]  
• Butler, M. O., Lee, J.-S., Ansen, S., Neuberg, D., Hodi, F. S., Murray, A. P., Drury, L., Berezovskaya, A., Mulligan, R. C., Nadler, L. M., Hirano, N. (2007). Long-Lived Antitumor CD8+ Lymphocytes for Adoptive Therapy Generated Using an Artificial Antigen-Presenting Cell. Clin. Cancer Res. 13: 1857-1867 [Abstract] [Full Text]  
• Walton, S. M., Gerlinger, M., de la Rosa, O., Nuber, N., Knights, A., Gati, A., Laumer, M., Strauss, L., Exner, C., Schafer, N., Urosevic, M., Dummer, R., Tiercy, J.-M., Mackensen, A., Jaeger, E., Levy, F., Knuth, A., Jager, D., Zippelius, A. (2006). Spontaneous CD8 T Cell Responses against the Melanocyte Differentiation Antigen RAB38/NY-MEL-1 in Melanoma Patients. J. Immunol. 177: 8212-8218 [Abstract] [Full Text]  
• Menzel, O., Migliaccio, M., Goldstein, D. R., Dahoun, S., Delorenzi, M., Rufer, N. (2006). Mechanisms Regulating the Proliferative Potential of Human CD8+ T Lymphocytes Overexpressing Telomerase. J. Immunol. 177: 3657-3668 [Abstract] [Full Text]  
• Migliaccio, M., Alves, P. M. S., Romero, P., Rufer, N. (2006). Distinct Mechanisms Control Human Naive and Antigen-Experienced CD8+ T Lymphocyte Proliferation. J. Immunol. 176: 2173-2182 [Abstract] [Full Text]  
• Pittet, M. J., Gati, A., Le Gal, F.-A., Bioley, G., Guillaume, P., de Smedt, M., Plum, J., Speiser, D. E., Cerottini, J.-C., Dietrich, P.-Y., Romero, P., Zippelius, A. (2006). Ex Vivo Characterization of Allo-MHC-Restricted T Cells Specific for a Single MHC-Peptide Complex. J. Immunol. 176: 2330-2336 [Abstract] [Full Text]  
• Reddy, J., Illes, Z., Zhang, X., Encinas, J., Pyrdol, J., Nicholson, L., Sobel, R. A., Wucherpfennig, K. W., Kuchroo, V. K. (2004). Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 101: 15434-15439 [Abstract] [Full Text]  
• Lonchay, C., van der Bruggen, P., Connerotte, T., Hanagiri, T., Coulie, P., Colau, D., Lucas, S., Van Pel, A., Thielemans, K., van Baren, N., Boon, T. (2004). Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen. Proc. Natl. Acad. Sci. USA 101: 14631-14638 [Abstract] [Full Text]  
• Meidenbauer, N., Zippelius, A., Pittet, M. J., Laumer, M., Vogl, S., Heymann, J., Rehli, M., Seliger, B., Schwarz, S., Gal, F.-A. L., Dietrich, P. Y., Andreesen, R., Romero, P., Mackensen, A. (2004). High Frequency of Functionally Active Melan-A-Specific T Cells in a Patient with Progressive Immunoproteasome-Deficient Melanoma. Cancer Res. 64: 6319-6326 [Abstract] [Full Text]  
• Savage, P., Gao, L., Vento, K., Cowburn, P., Man, S., Steven, N., Ogg, G., McMichael, A., Epenetos, A., Goulmy, E., Stauss, H. J. (2004). Use of B cell-bound HLA-A2 class I monomers to generate high-avidity, allo-restricted CTLs against the leukemia-associated protein Wilms tumor antigen. Blood 103: 4613-4615 [Abstract] [Full Text]  
• Zippelius, A., Batard, P., Rubio-Godoy, V., Bioley, G., Lienard, D., Lejeune, F., Rimoldi, D., Guillaume, P., Meidenbauer, N., Mackensen, A., Rufer, N., Lubenow, N., Speiser, D., Cerottini, J.-C., Romero, P., Pittet, M. J. (2004). Effector Function of Human Tumor-Specific CD8 T Cells in Melanoma Lesions: A State of Local Functional Tolerance. Cancer Res. 64: 2865-2873 [Abstract] [Full Text]  
• Rothenfusser, S., Hornung, V., Ayyoub, M., Britsch, S., Towarowski, A., Krug, A., Sarris, A., Lubenow, N., Speiser, D., Endres, S., Hartmann, G. (2004). CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8+ T-cell responses in vitro. Blood 103: 2162-2169 [Abstract] [Full Text]  
• Zippelius, A., Bioley, G., Le Gal, F.-A., Rufer, N., Brandes, M., Batard, P., De Smedt, M., Plum, J., Speiser, D. E., Cerottini, J.-C., Dietrich, P.-Y., Romero, P., Pittet, M. J. (2004). Human Thymus Exports Naive CD8 T Cells That Can Home to Nonlymphoid Tissues. J. Immunol. 172: 2773-2777 [Abstract] [Full Text]  
• Fleischer, K., Schmidt, B., Kastenmuller, W., Busch, D. H., Drexler, I., Sutter, G., Heike, M., Peschel, C., Bernhard, H. (2004). Melanoma-Reactive Class I-Restricted Cytotoxic T Cell Clones Are Stimulated by Dendritic Cells Loaded with Synthetic Peptides, but Fail to Respond to Dendritic Cells Pulsed with Melanoma-Derived Heat Shock Proteins In Vitro. J. Immunol. 172: 162-169 [Abstract] [Full Text]  
• Salio, M., Dulphy, N., Renneson, J., Herbert, M., McMichael, A., Marchant, A., Cerundolo, V. (2003). Efficient priming of antigen-specific cytotoxic T lymphocytes by human cord blood dendritic cells. Int Immunol 15: 1265-1273 [Abstract] [Full Text]  
• Rufer, N., Zippelius, A., Batard, P., Pittet, M. J., Kurth, I., Corthesy, P., Cerottini, J.-C., Leyvraz, S., Roosnek, E., Nabholz, M., Romero, P. (2003). Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions. Blood 102: 1779-1787 [Abstract] [Full Text]  
• Pittet, M. J., Rubio-Godoy, V., Bioley, G., Guillaume, P., Batard, P., Speiser, D., Luescher, I., Cerottini, J.-C., Romero, P., Zippelius, A. (2003). {alpha}3 Domain Mutants of Peptide/MHC Class I Multimers Allow the Selective Isolation of High Avidity Tumor-Reactive CD8 T Cells. J. Immunol. 171: 1844-1849 [Abstract] [Full Text]  
• Geginat, J., Lanzavecchia, A., Sallusto, F. (2003). Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines. Blood 101: 4260-4266 [Abstract] [Full Text]  
• Dietrich, P.-Y., Le Gal, F.-A., Dutoit, V., Pittet, M. J., Trautman, L., Zippelius, A., Cognet, I., Widmer, V., Walker, P. R., Michielin, O., Guillaume, P., Connerotte, T., Jotereau, F., Coulie, P. G., Romero, P., Cerottini, J.-C., Bonneville, M., Valmori, D. (2003). Prevalent Role of TCR {alpha}-Chain in the Selection of the Preimmune Repertoire Specific for a Human Tumor-Associated Self-Antigen. J. Immunol. 170: 5103-5109 [Abstract] [Full Text]  
• Carrabba, M. G., Castelli, C., Maeurer, M. J., Squarcina, P., Cova, A., Pilla, L., Renkvist, N., Parmiani, G., Rivoltini, L. (2003). Suboptimal Activation of CD8+ T Cells by Melanoma-derived Altered Peptide Ligands: Role of Melan-A/MART-1 Optimized Analogues. Cancer Res. 63: 1560-1567 [Abstract] [Full Text]  
• Ayyoub, M., Zippelius, A., Pittet, M. J., Rimoldi, D., Valmori, D., Cerottini, J.-C., Romero, P., Lejeune, F., Lienard, D., Speiser, D. E. (2003). Activation of Human Melanoma Reactive CD8+ T Cells by Vaccination with an Immunogenic Peptide Analog Derived from Melan-A/Melanoma Antigen Recognized by T Cells-1. Clin. Cancer Res. 9: 669-677 [Abstract] [Full Text]  
• Mantovani, S., Palermo, B., Garbelli, S., Campanelli, R., Robustelli della Cuna, G., Gennari, R., Benvenuto, F., Lantelme, E., Giachino, C. (2002). Dominant TCR-{alpha} Requirements for a Self Antigen Recognition in Humans. J. Immunol. 169: 6253-6260 [Abstract] [Full Text]  
• Mandruzzato, S., Rossi, E., Bernardi, F., Tosello, V., Macino, B., Basso, G., Chiarion-Sileni, V., Rossi, C. R., Montesco, C., Zanovello, P. (2002). Large and Dissimilar Repertoire of Melan-A/MART-1-Specific CTL in Metastatic Lesions and Blood of a Melanoma Patient. J. Immunol. 169: 4017-4024 [Abstract] [Full Text]  
• Dutoit, V., Rubio-Godoy, V., Pittet, M. J., Zippelius, A., Dietrich, P.-Y., Legal, F. A., Guillaume, P., Romero, P., Cerottini, J.-C., Houghten, R. A., Pinilla, C., Valmori, D. (2002). 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. 196: 207-216 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS