Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies.
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.
Trojan
A
A
Department of Adult Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
Schultze
J L
JL
Witzens
M
M
Vonderheide
R H
RH
Ladetto
M
M
Donovan
J W
JW
Gribben
J G
JG
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*
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D010455:Peptides