Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein prostein.
The development of T-cell-based immunotherapies of cancer largely depends on the availability of tumour-associated antigens capable of eliciting tumour-directed cytotoxic T-cell responses. In prostate cancer, the number of antigens defined as suitable targets of cytotoxic T lymphocytes (CTLs) is still limited. Recently, prostein was identified as a transmembrane protein that is highly restricted to prostate tissues. In our study, prostein transcripts were found to be abundant in both malignant and nonmalignant prostate tissue samples. To identify immunogenic CD8+ T-cell epitopes, human leucocyte antigen-A(*)0201-binding peptides were selected from the amino-acid sequence of prostein and were used for the in vitro stimulation of CD8+ T lymphocytes. Specific CTLs were raised against the prostein-derived peptide CLAAGITYV that were capable of lysing prostate cancer cells, indicating that this peptide is naturally generated by tumour cells. Our data suggest that prostein is a suitable candidate to be included in a T-cell-based immunotherapy of prostate cancer.
Kiessling
A
A
Institute of Immunology, Medical Faculty, Technical University of Dresden, Fetscherstr. 74, Dresden 01307, Germany.
Stevanovic
S
S
Füssel
S
S
Weigle
B
B
Rieger
M A
MA
Temme
A
A
Rieber
E P
EP
Schmitz
M
M
D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002857:Chromium / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D015234:HLA-A Antigens / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D020014:K562 Cells; D008297:Male; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011467:Prostate / Q000276:immunology / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000276:immunology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C422655:prostein; D002857:Chromium; D017430:Prostate-Specific Antigen