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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-4-19
pubmed:abstractText
The development of immunotherapy for prostate cancer based on the induction of autoimmunity to prostate tissue is very attractive because prostate is not a vital organ beyond the reproductive years. CD4 T cells play an important role in the development of antitumor immune responses, yet the identification of naturally processed MHC Class II-restricted epitopes derived from prostate differentiation antigens has not been described. To facilitate the search for prostate-specific antigen (PSA)-derived MHC class II-restricted peptides, we immunized mice transgenic for HLA-DRB1*1501 with human PSA and showed a robust dose-dependent immune response to the antigen. Screening a library of overlapping 20-mer peptides that span the entire PSA sequence identified two 20-mer peptides, PSA(171-190) and PSA(221-240), which were responsible for this reactivity. Immunization of DR2b transgenic mice with these peptides induced specific responses to the peptide and whole PSA. Identified peptides were used to stimulate CD4 T cells from HLA-DRB1*1501+ patients with a rare condition, granulomatous prostatitis, and who seem to have a preexisting immune response directed against the prostate gland. We previously showed a linkage of granulomatous prostatitis to HLA-DRB1*1501, suggesting that this disease may have an autoimmune etiology. Peptide-specific CD4 T-cell lines were generated from the peripheral blood of these patients as well as one patient with prostate cancer. These lines also recognized whole, processed PSA in the context of HLA-DRB1*1501. This study will be instrumental in understanding the interaction between circulating self-reactive T cells, organ-specific autoimmunity, and antitumor immune response. The use of these peptides for the immunotherapy of prostate cancer is under investigation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2853-61
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15837732-Amino Acid Sequence, pubmed-meshheading:15837732-Animals, pubmed-meshheading:15837732-CD4-Positive T-Lymphocytes, pubmed-meshheading:15837732-Cell Line, pubmed-meshheading:15837732-Cell Proliferation, pubmed-meshheading:15837732-Dose-Response Relationship, Drug, pubmed-meshheading:15837732-Epitopes, pubmed-meshheading:15837732-Epitopes, T-Lymphocyte, pubmed-meshheading:15837732-Female, pubmed-meshheading:15837732-HLA-DR Antigens, pubmed-meshheading:15837732-HLA-DR2 Antigen, pubmed-meshheading:15837732-HLA-DRB1 Chains, pubmed-meshheading:15837732-Humans, pubmed-meshheading:15837732-Interferon-gamma, pubmed-meshheading:15837732-Male, pubmed-meshheading:15837732-Mice, pubmed-meshheading:15837732-Mice, Transgenic, pubmed-meshheading:15837732-Molecular Sequence Data, pubmed-meshheading:15837732-Oligopeptides, pubmed-meshheading:15837732-Prostate-Specific Antigen
pubmed:year
2005
pubmed:articleTitle
Identification of HLA-DRB1*1501-restricted T-cell epitopes from prostate-specific antigen.
pubmed:affiliation
Urology Section, VA Maryland Health Care System, and Division of Urology, University of Maryland School of Medicine, Baltimore, Maryland 21202, USA. eklyushnenkova@smail.umaryland.edu
pubmed:publicationType
Journal Article