Abstract
Although the idiotypic structures of immunoglobulin from malignant B cells were the first tumor-specific determinants recognized, and clinical vaccination trials have demonstrated induction of tumor-specific immunity, the function of immunoglobulin-specific CD8+ cytotoxic T lymphocytes in tumor rejection remains elusive. Here, we combined bioinformatics and a T cell-expansion system to identify human immunoglobulin-derived peptides capable of inducing cytotoxic T-lymphocyte responses. Immunogenic peptides were derived from framework regions of the variable regions of the immunoglobulin that were shared among patients. Human-leukocyte-antigen-matched and autologous cytotoxic T lymphocytes specific for these peptides killed primary malignant B cells, demonstrating that malignant B cells are capable of processing and presenting such peptides. Targeting shared peptides to induce T-cell responses might further improve current vaccination strategies in B-cell malignancies.
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Acknowledgements
We thank L.M. Nadler, C. Janeway Jr., K.W. Wucherpfennig and K.S. Anderson for reading the manuscript. We thank G. Dranoff for discussions and D. Neuberg for statistical assistance. Technical assistance for immunoglobulin sequencing was provided by T. Poor and D. Bowers, and for T-cell cultures, by M. Bedor and D. Schnipper. This work was supported by grants PO1 CA 66996, CA78378 and CA81534 from the National Institutes of Health. J.L.S. is a Special Fellow of the Leukemia and Lymphoma Society of America. M.W. is supported by a grant from the Deutsche Krebshilfe und Dr. Mildred Scheel Stiftung. R.H.V. is supported by a grant from the Doris Duke Charitable Foundation.
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Trojan, A., Schultze, J., Witzens, M. et al. Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies. Nat Med 6, 667–672 (2000). https://doi.org/10.1038/76243
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DOI: https://doi.org/10.1038/76243
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