Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed i
Author: ["Andreas Trojan","Joachim L. Schultze","Mathias Witzens","Robert H. Vonderheide","Marco Ladetto","John W. Donovan","John G. Gribben"]
Publication: Nature Medicine
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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.
Cite this article
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