PMID- 20886538
OWN - NLM
STAT- MEDLINE
DCOM- 20110527
LR  - 20151119
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Linking)
VI  - 71
IP  - 6
DP  - 2011 May
TI  - CD4 T-Cell-mediated immune response to prostatic proteins in HLA-DRB1*1503 
      transgenic mice and identification of a novel HLA-DRB1*1503-restricted T-cell 
      epitope from human prostatic acid phosphatase.
PG  - 561-6
LID - 10.1002/pros.21271 [doi]
AB  - BACKGROUND: Transgenic mice engineered to express human leukocyte antigen (HLA) 
      alleles are widely used for identification of immunogenic and naturally processed 
      epitopes. Using HLA-DRB1*1501 (DR2b) transgenic mice, we have previously 
      identified epitopes from two prostatic antigens, prostate-specific antigen (PSA) 
      and prostatic acid phosphatase (PAP). These antigens are implicated in the 
      development of autoimmunity in the prostate and also are considered promising 
      targets for prostate cancer immunotherapy. HLA-DRB1*1501 is the most common DR15 
      allele in Caucasians, while HLA-DRB1*1503 is the most common in African 
      Americans. Hence characterization of peptide immunogenicity for these alleles is 
      important for the development of prostate cancer immunotherapy in white and black 
      patients. METHODS: HLA-DRB1*1501 or HLA-DRB1*1503 transgenic mice were immunized 
      with human PSA or PAP. Libraries of overlapping 20-mer peptides spanning the 
      entire sequences of these proteins were screened by IFN-gamma ELISPOT assay. RESULTS: 
      PSA and PAP peptides that were previously identified in HLA-DRB1*1501 tg mice 
      were immunogenic in HLA-DR1503 tg mice and induced CD4 T-cell response against 
      whole processed PSA or PAP respectively. However, the hierarchy of the 
      immunodominance among the peptides differed significantly between strains. Using 
      HLA-DRB1*1503 tg mice, a novel immunogenic and naturally processed 20-mer 
      peptide, PAP (233-252) has been identified that showed no reactivity in 
      HLA-DRB1*1501 tg mice. CONCLUSIONS: Our data demonstrate a disparity in CD4 
      T-cell immune reactivity to PSA and PAP between HLA-DRB1*1501 and -DRB1*1503 
      alleles in HLA transgenic mouse models. It is possible that such immunological 
      differences could contribute to racial disparity in prostate cancer outcome.
CI  - Copyright (c) 2010 Wiley-Liss, Inc.
FAU - Klyushnenkova, Elena N
AU  - Klyushnenkova EN
AD  - VA Maryland Health Care System, Department of Surgery, University of Maryland 
      School of Medicine, Baltimore, Maryland 21201, USA. 
      eklyushnenkova@smail.umaryland.edu
FAU - Alexander, Richard B
AU  - Alexander RB
LA  - eng
PT  - Journal Article
DEP - 20100930
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Peptide Library)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.1.3.2 (Acid Phosphatase)
RN  - EC 3.1.3.2 (prostatic acid phosphatase)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Acid Phosphatase
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/cytology/enzymology/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - HLA-DR Antigens/genetics/*immunology
MH  - HLA-DRB1 Chains
MH  - Immunodominant Epitopes/immunology
MH  - Interferon-gamma/analysis/immunology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Peptide Library
MH  - Prostate/cytology/enzymology/*immunology
MH  - Prostate-Specific Antigen/*immunology
MH  - Protein Tyrosine Phosphatases/*immunology
EDAT- 2010/10/05 06:00
MHDA- 2011/05/28 06:00
CRDT- 2010/10/02 06:00
PHST- 2010/06/14 00:00 [received]
PHST- 2010/08/16 00:00 [accepted]
PHST- 2010/10/02 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2011/05/28 06:00 [medline]
AID - 10.1002/pros.21271 [doi]
PST - ppublish
SO  - Prostate. 2011 May;71(6):561-6. doi: 10.1002/pros.21271. Epub 2010 Sep 30.