Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase.
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)-gamma 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.
Klyushnenkova
Elena N
EN
Division of Urology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. eklyushnenkova@smail.umaryland.edu
Kouiavskaia
Diana V
DV
Kodak
James A
JA
Vandenbark
Arthur A
AA
Alexander
Richard B
RB
D000135:Acid Phosphatase; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D015802:HLA-DR2 Antigen / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000235:genetics / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000517:prevention & control; D011472:Prostatitis / Q000235:genetics / Q000276:immunology; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000235:genetics / Q000276:immunology*
D019496:Cancer Vaccines; D000939:Epitopes; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D010455:Peptides; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases