Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies

Andreas Trojan, Joachim L. Schultze, Mathias Witzens, Robert H. Vonderheide, Marco Ladetto, John W. Donovan, John G. Gribben

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

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- antigenmatched 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.

Lingua originaleInglese
pagine (da-a)667-672
Numero di pagine6
RivistaNature Medicine
Volume6
Numero di pubblicazione6
DOI
Stato di pubblicazionePubblicato - giu 2000
Pubblicato esternamente

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