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International Immunology Advance Access originally published online on October 31, 2006
International Immunology 2006 18(12):1707-1718; doi:10.1093/intimm/dxl105
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Immunogenic HLA-B7-restricted peptides of hTRT

Xochitl Cortez-Gonzalez1, John Sidney2, Olivier Adotevi3, Alessandro Sette2, Frederick Millard1, Francois Lemonnier3, Pierre Langlade-Demoyen3 and Maurizio Zanetti1

1 Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0837, USA
2 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, La Jolla, CA 92121, USA
3 Laboratoire d'Immunite Cellulaire Anti-Virale, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris, France

Correspondence to: M. Zanetti; E-mail: mzanetti{at}ucsd.edu

Telomerase reverse transcriptase (TRT) is the first bona fide common tumor antigen. While several 9mer peptides of the human TRT have been identified for HLA-A2, little information exists on peptides for the remaining HLA types. Here, we used a multi-step approach to select and characterize a panel of HLA-B7 9mer peptides as candidate immunogens. In sequence, we used algorithm-based predictions, in vivo immunization of HLA-B7 transgenic (Tg) mice, in vitro immunization of human blood lymphocytes from two normal donors and two cancer patients, in vivo processing in HLA-B7 Tg mice and HLA-B7 supertype binding. We found a correlation between the in vivo immunogenicity and the actual HLA-B7 binding avidity of the seven predicted peptides. Furthermore, endogenous processing correlated with in vitro immunogenicity in human PBMC and HLA-B7 supertype binding. Peptide 1123LPSDFKTIL1131 (p1123) with the wider spectrum of supertype binding displayed the highest immunogenicity overall and was endogenously processed in several human lymphoblastoid cells. Since no single step of the screening/selection process could substitute for the whole approach, we conclude that the identification of MHC class I-restricted peptides for potential vaccination of cancer patients remains, by and large, an empirical process.

Keywords: cancer, supertype, telomerase

Transmitting editor: S. Hedric


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