PMID- 15935893
OWN - NLM
STAT- MEDLINE
DCOM- 20051212
LR  - 20111117
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 66
IP  - 5
DP  - 2005 May
TI  - Identification of HLA-DQalpha and -DRbeta residues associated with susceptibility 
      and protection to epithelial ovarian cancer.
PG  - 554-62
AB  - Substantial evidence has been accumulated suggesting that T cells in patients 
      with epithelial ovarian carcinoma (EOC) exhibit an antigen-driven immune response 
      directed against the tumor cells. In the context of human leukocyte antigen 
      (HLA), this suggests its possible involvement in the disease. Therefore, we 
      examined the distribution of the HLA-DRB1*, -DQA1*, and -DQB1* alleles in 47 
      patients with EOC and 67 healthy Caucasian women. The frequency of D(70) and 
      E(71) polymorphic residues of the DRB1 alleles was significantly reduced in EOC 
      patients versus controls (pD(70)E(71) = 0.009), suggesting a protective role 
      against the disease. The DQalpha residues R(52) and Y(11)R(55) were increased in 
      the patients (p = 0.008 and 0.012, respectively). Because residues 11 and 55 
      participate in the formation of pocket 1, they may be functionally important 
      amino acid positions that influence disease susceptibility. The frequency of the 
      DQalpha susceptibility epitope (R(52)Y(11)R(55)) among the 
      DRbetaD(70)E(71)-positive EOC patients was increased when compared with 
      DRbetaD(70)E(71)-positive controls (EOC, 100%; control, 52%; p = 0.028). Among 
      individuals without the DQalpha susceptibility epitope, the distribution of 
      DRbetaD(70)E(71)-positive cases was significantly different between EOC patients 
      and controls (EOC, 0%; control, 60%; p = 0.039). Therefore, it appears that the 
      presence of DQalpha susceptibility elements overrides the protective effect of 
      the DRbetaD(70)E(71) epitope and suggests an interactive relationship between 
      DRbeta and DQalpha epitopes that may be of importance for disease susceptibility. 
      Because positions DRbeta 70,71 and DQalpha 52 have been implicated in immunologic 
      diseases, it is likely that besides being critical for T-cell recognition, they 
      may also play a role in T-cell development and acquisition of the T-cell 
      repertoire.
FAU - Monos, Dimitri S
AU  - Monos DS
AD  - Department of Pediatrics, University of Pennsylvania School of Medicine, 
      Philadelphia, PA, USA.
FAU - Pappas, John
AU  - Pappas J
FAU - Magira, Eleni E
AU  - Magira EE
FAU - Gaughan, John
AU  - Gaughan J
FAU - Aplenc, Richard
AU  - Aplenc R
FAU - Sakkas, Lazaros
AU  - Sakkas L
FAU - Freedman, Ralph
AU  - Freedman R
FAU - Reveille, John D
AU  - Reveille JD
FAU - Platsoucas, Chris D
AU  - Platsoucas CD
LA  - eng
GR  - CA57884/CA/NCI NIH HHS/United States
GR  - T32 AI07101/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050303
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Disease Susceptibility/immunology
MH  - Epitopes, T-Lymphocyte/genetics/immunology
MH  - Female
MH  - Gene Frequency/genetics/immunology
MH  - Genetic Predisposition to Disease/*genetics
MH  - HLA-DQ Antigens/*genetics/immunology
MH  - HLA-DQ alpha-Chains
MH  - HLA-DR Antigens/*genetics/immunology
MH  - Histocompatibility Testing
MH  - Humans
MH  - Molecular Sequence Data
MH  - Neoplasms, Glandular and Epithelial/*genetics/immunology
MH  - Ovarian Neoplasms/*genetics/immunology
MH  - Polymorphism, Genetic/genetics/immunology
EDAT- 2005/06/07 09:00
MHDA- 2005/12/15 09:00
CRDT- 2005/06/07 09:00
PHST- 2004/12/13 00:00 [received]
PHST- 2005/01/19 00:00 [accepted]
PHST- 2005/06/07 09:00 [pubmed]
PHST- 2005/12/15 09:00 [medline]
PHST- 2005/06/07 09:00 [entrez]
AID - S0198-8859(05)00032-7 [pii]
AID - 10.1016/j.humimm.2005.01.019 [doi]
PST - ppublish
SO  - Hum Immunol. 2005 May;66(5):554-62. doi: 10.1016/j.humimm.2005.01.019. Epub 2005 
      Mar 3.