Premium
Identification of HLA‐DRB1*1501‐restricted T‐cell epitopes from human prostatic acid phosphatase
Author(s) -
Klyushnenkova Ele.,
Kouiavskaia Diana V.,
Kodak James A.,
Vandenbark Arthur A.,
Alexander Richard B.
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20575
Subject(s) - prostatic acid phosphatase , epitope , elispot , human leukocyte antigen , immunology , immunotherapy , antigen , autoimmunity , immune system , prostate cancer , t cell , biology , cancer , medicine , cancer research
BACKGROUND The crucial role of CD4 T‐cells in anti‐tumor immune response is widely recognized, yet the identification of HLA class II‐restricted epitopes derived from tumor antigens has lagged behind compared to class I epitopes. This is particularly true for prostate cancer. Based on the hypothesis that successful cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T‐cell epitopes derived from prostatic proteins that are restricted by human leukocyte antigen (HLA)‐DRB1*1501 , an allele associated with granulomatous prostatitis (GP), a disease that may have an autoimmune etiology. One of the antigens implicated in the development of autoimmunity in the prostate is prostatic acid phosphatase (PAP), which is also considered a promising target for prostate cancer immunotherapy. METHODS We immunized transgenic (tg) mice engineered to express HLA‐DRB1*1501 with human PAP. A library of overlapping 20‐mer peptides spanning the entire human PAP sequence was screened in vitro for T‐cell recognition by proliferative and interferon (IFN)‐γ enzyme‐linked immunosorbent spot (ELISPOT) assays. RESULTS We identified two 20‐mer peptides, PAP (133–152), and PAP (173–192), that were immunogenic and naturally processed from whole PAP in HLA‐DRB1*1501 tg mice. These peptides were also capable of stimulating CD4 T lymphocytes from HLA‐DRB1*1501 ‐positive patients with GP and normal donors. CONCLUSIONS These peptides can be used for the design of a new generation of peptide‐based vaccines against prostate cancer. The study can also be helpful in understanding the role of autoimmunity in the development of some forms of chronic prostatitis. Prostate 67: 1019–1028, 2007. © 2007 Wiley‐Liss, Inc.