title: Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies.
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.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Trojan
authors.forename: J L
authors.initials: JL
authors.lastname: Schultze
authors.forename: M
authors.initials: M
authors.lastname: Witzens
authors.forename: R H
authors.initials: RH
authors.lastname: Vonderheide
authors.forename: M
authors.initials: M
authors.lastname: Ladetto
authors.forename: J W
authors.initials: JW
authors.lastname: Donovan
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D019295:Computational Biology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D007945:Leukemia, Lymphoid / Q000276:immunology*; D008224:Lymphoma, Follicular / Q000276:immunology; D020522:Lymphoma, Mantle-Cell / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D010455:Peptides