Abstract
Cytotoxic T-cells are the most important effector cells in immune responses against tumors. The identification of tumor-associated epitopes for these cells, therefore, has become a key aspect of the development of cancer vaccines. Here, we describe a new approach to the determination of tumor-associated T-cell epitopes which employs combinatorial peptide libraries with singly defined sequence positions in a randomized context. The analysis of the responses of a T-cell clone to these libraries yields the amino acid constituents of the epitope which can be combined to obtain mimotopes that are suitable as vaccine antigens for the induction of tumor-specific responses.
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Renkvist, N., Castelli, C., Robbins, P. F., and Parmiani, G. (2001) A listing of human tumor antigens recognized by T-cells. Cancer Immunol Immunother. 50, 3–15.
Castelli, C., Storkus, W. J., Maeurer, M. J., et al. (1995) Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes. J. Exp. Med. 181, 363–368.
Tureci, O., Sahin, U., Schobert, I., et al. (1996) The SSX-2 gene, which is involved in the t(X; 18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40. Cancer Res. 56, 4766–4772.
De Plaen, E., Lurquin, C., Brichard, V., et al. (1997) Cloning of genes coding for antigens recognized by cytolytic T lymphocytes. In: The Immunology Methods Manual. (Lefkovits, I., ed.), Academic Press Ltd., New York, pp. 692–718.
Walden, P., Wiesmüller, K. H. and Jung, G. (1995) Elucidation of T-cell epitopes: A synthetic approach with random peptide libraries. Biochem. Soc. Trans. 23, 678–681.
Rammensee, H. G., Bachmann, J. and Stevanovic, S. (1997) MHC Ligands and Peptide Motifs. Landes Bioscience, Georgetown, TX.
Gundlach, B. R., Wiesmüller, K. H., Junt, T., et al. (1996) Determination of T-cell epitopes with random peptide libraries. J. Immunol. Methods 192, 149–155.
Walden, P. (1996) T-cell epitope determination. Curr. Opin. Immunol. 8, 68–74.
Rubio-Godoy, V., Ayyoub, M., Dutoit, V., et al. (2002) Combinatorial peptide library-based identification of peptide ligands for tumor-reactive cytolytic T lymphocytes of unknown specificity. Eur. J. Immunol. 32, 2292–2299.
Furka, A. (1996) Chemical synthesis of peptide libraries. In: Combinatorial Peptide and Nonapeptide Libraries. (Jung, G. ed.), VCH Verlagsgesellschaft mbH, Weinheim, Germany.
Kern, F., Surel, I. P., Brock, C., et al. (1998) T-cell epitope mapping by flow cytometry. Nat. Med. 4, 975–978.
Linnemann, T., Tumenjargal, S., Gellrich, S., et al. (2001) Mimotopes for tumor-specific T lymphocytes in human cancer determined with combinatorial peptide libraries. Eur. J. Immunol. 1, 156–165.
Hiemstra, H. S., Duinkerken, G., Benckhuijsen, W. E., et al. (1997) The identification of CD4+ T-cell epitopes with dedicated synthetic peptide libraries. Proc. Nat. Acad. Sci. USA. 94, 10,313–10,318.
Wilson, D. B., Pinilla, C., Wilson, D. H., et al. (1999) Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4+ T-cells and induce T-cell responses to native peptide ligands. J. Immunol. 163, 6424–6434.
Gundlach, B. R., Wiesmüller, K.-H., Junt, T., et al. (1996) Specificity and degeneracy of minor histocompatibility antigen-specific MHC-restricted cytotoxic T lymphocytes. J. Immunol. 156, 3645–3651.
Boesteanu, A., Brehm, M., Mylin, L. M., et al. (1998) A molecular basis for how a single TCR interfaces multiple Ligands. J. Immunol. 161, 4719–4727.
Hemmer, B., Fleckenstein, B. T., Vergelli, M., et al. (1997) Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T-cell clone. J. Exp. Med. 185, 1651–1659.
Udaka, K., Wiesmüller, K.-H., Kienle, S., et al. (1996) Self-MHC restricted peptides recognized by an allo MHC-responsive CTL clone. J. Immunol. 157, 670–678.
Dressel, A., Chin, J. L., Sette, A., et al. (1997) Autoantigen recognition by human CD8 T-cell clones: enhanced agonist response induced by altered peptide ligands. J. Immunol. 159, 4943–4951.
La Rosa, C., Krishnan, R., Markel, S., et al. (2001) Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries. Blood 97, 1776–1786.
Hemmer, B., Pinilla, C., Gran, B., et al. (2000) Contribution of individual amino acids within MHC molecule or antigenic peptide to TCR ligand potency. J. Immunol. 164, 861–871.
Udaka, K., Wiesmüller, K. H., Kienle, S., et al. (1995) Tolerance to amino acid variations in peptides binding to the major histocompatibility complex class I protein H-2Kb. J. Biol. Chem. 270, 24,130–24,134.
Jung, C., Kalbus, M., Fleckenstein, B., et al. (1998) New ligands for HLA DRB1 *0301 by random selection of favourable amino acids ranked by competition studies with undecapeptide amide sublibraries. J. Immunol. Methods 219, 139–149.
Agnes, M. C., Tan, A., Jordens, R., et al. (1998) Strongly increased efficiency of altered peptide ligands by mannosylation. Int. Immunol. 10, 1299–1304.
Ostankovitch, M., Guichard, G., Connan, F., et al. (1998) A partially modified retro-inverso pseudopeptide modulates the cytokine profile of CTL specific for an influenza virus epitope. J. Immunol. 161, 200–208.
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Sherev, T., Wiesmüller, KH. & Walden, P. Mimotopes of tumor-associated T-cell epitopes for cancer vaccines determined with combinatorial peptide libraries. Mol Biotechnol 25, 53–61 (2003). https://doi.org/10.1385/MB:25:1:53
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DOI: https://doi.org/10.1385/MB:25:1:53