PMID- 19206073
OWN - NLM
STAT- MEDLINE
DCOM- 20090501
LR  - 20111117
IS  - 1075-2617 (Print)
IS  - 1075-2617 (Linking)
VI  - 15
IP  - 4
DP  - 2009 Apr
TI  - HLA-DQ7 beta(1) and beta(2) derived peptides as immunomodulators.
PG  - 296-304
LID - 10.1002/psc.1115 [doi]
AB  - Modulation of protein-protein interactions involved in the immune system by using 
      small molecular mimics of the contact interfaces may lead to the blockage of the 
      autoimmune response and the development of drugs for immunotherapy. The 
      nonpolymorphic beta-regions, exposed to the microenvironment, of the modeled 
      HLA-DQ7, which is genetically linked to autoimmune diseases, were determined. 
      Peptides 132-141 and 58-67, located at the beta(1) and beta(2) domains of 
      HLA-DQ7, respectively, were tested for their involvement in the interactions with 
      CD4(+) T lymphocytes. Linear, cyclic, and dimeric analogs that mimic the exposed 
      surfaces of HLA-DQ7 were designed and synthesized. Their immunosuppressory 
      activities, found in the secondary, humoral immune response to sheep erythrocytes 
      (SRBC) in mice in vitro, ranged from 11% to 53%. The significance of the total 
      charge of the peptides, the pattern of the hydrogen bonding, and the presence of 
      secondary structure were investigated in relation to the immunomodulatory effect 
      of the peptides. Two dimeric analogs of the HLA-DQ7 58-67 fragment, consisting of 
      the two monomers covalently linked by a polyethylene glycol (PEG) spacer, able to 
      mimic the superdimers, were also synthesized and studied. As the 58-67 segment is 
      located at the beta(1) region of HLA-DQ7, close to the major histocompatibility 
      complex (MHC) groove, one may assume that the 58-67 peptide could accommodate the 
      association between T-cell receptor (TCR) and human leukocyte antigen (HLA) by 
      activating a co-stimulatory molecule of the TCR/HLA interaction. This hypothesis 
      is supported by the confocal laser image of the fluorescein-labeled 58-67 peptide 
      and by the fact that it is an immunostimulator at low concentration.
FAU - Skarlas, Theodore
AU  - Skarlas T
AD  - Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
FAU - Panou-Pomonis, Eugenia
AU  - Panou-Pomonis E
FAU - Kluczyk, Alicja
AU  - Kluczyk A
FAU - Szewczuk, Zbigniew
AU  - Szewczuk Z
FAU - Zimecki, Michal
AU  - Zimecki M
FAU - Kosmopoulou, Aggeliki
AU  - Kosmopoulou A
FAU - Sakarellos-Daitsiotis, Maria
AU  - Sakarellos-Daitsiotis M
FAU - Sakarellos, Constantinos
AU  - Sakarellos C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pept Sci
JT  - Journal of peptide science : an official publication of the European Peptide 
      Society
JID - 9506309
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ7 antigen)
RN  - 0 (Immunologic Factors)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Female
MH  - HLA-DQ Antigens/*chemistry/immunology/pharmacology
MH  - Humans
MH  - Immunologic Factors/*chemical synthesis/chemistry/pharmacology
MH  - Lymphocytes/drug effects/immunology
MH  - Macrophages/drug effects/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Models, Molecular
MH  - Oligopeptides/chemical synthesis/chemistry/immunology/pharmacology
MH  - Peptide Fragments/chemical synthesis/chemistry/immunology/pharmacology
MH  - Protein Conformation
MH  - Spectrometry, Mass, Electrospray Ionization
EDAT- 2009/02/12 09:00
MHDA- 2009/05/02 09:00
CRDT- 2009/02/12 09:00
PHST- 2009/02/12 09:00 [entrez]
PHST- 2009/02/12 09:00 [pubmed]
PHST- 2009/05/02 09:00 [medline]
AID - 10.1002/psc.1115 [doi]
PST - ppublish
SO  - J Pept Sci. 2009 Apr;15(4):296-304. doi: 10.1002/psc.1115.