Identification of a promiscuous HLA DR-restricted T-cell epitope derived from the inhibitor of apoptosis protein survivin.
The inhibitor of apoptosis protein survivin is a promising tumor-associated antigen specifically recognized by CD8+ cytotoxic effector T-lymphocytes (CTL). To improve current vaccines that aim to induce survivin-specific CTL, it is necessary to study the role of CD4+ T-helper (TH) and CD4+ T-regulatory (Treg) cells. Because both TH and Treg cells recognize antigens in the context of HLA-class II molecules, identification of HLA class II-associated peptide epitopes from survivin is required. Here, we analyzed T-cell responses against survivin using synthetic peptides predicted to serve as HLA-DR-restricted epitopes. Six peptides were shown to induce CD4+ T-cell responses, restricted by HLA-DR molecules. For one peptide epitope, SVN10, T-cell clones were demonstrated to be capable of recognizing naturally processed antigen. SVN10-specific T cells could be stimulated from the blood of healthy individuals and cancer patients with multiple HLA-DR genotypes. Thus the identified SVN10 epitope can be used to study the role of CD4+ TH and Treg cells in immune responses and possibly be included in a multivalent peptide vaccine against survivin.
Piesche
Matthias
M
Department of Hematology and Oncology, Georg-August-University Göttingen, Göttingen, Germany.
Hildebrandt
York
Y
Zettl
Florian
F
Chapuy
Björn
B
Schmitz
Marc
M
Wulf
Gerald
G
Trümper
Lorenz
L
Schroers
Roland
R
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000077022:Survivin; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D000077022:Survivin