PMID- 20105447
OWN - NLM
STAT- MEDLINE
DCOM- 20100709
LR  - 20111117
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 71
IP  - 5
DP  - 2010 May
TI  - Design of new high-affinity peptide ligands for human leukocyte antigen-DQ2 using 
      a positional scanning peptide library.
PG  - 475-81
LID - 10.1016/j.humimm.2010.01.021 [doi]
AB  - Human leukocyte antigen (HLA)-DQ2 (DQA1 x 0501/DQB1 x 0201) is associated with 
      several immune disorders, including celiac disease, which is caused by an 
      inappropriate T-cell response to gluten. Interference with peptide presentation 
      by HLA-DQ2, for example, by the use of peptide blockers, is a possible treatment 
      strategy for such HLA-associated disorders. A successful implementation of this 
      strategy will depend on the identification of ligands that bind much better to 
      HLA-DQ2 than the disease related epitopes. We have used a positional scanning 
      nonapeptide library to determine the optimal amino acids for each position of the 
      HLA-DQ2 binding frame. By combining the optimal residues in each position, we 
      were able to design high affinity binders to HLA-DQ2. Interestingly, the 
      decapeptide with highest affinity was composed of the most favorable residues in 
      each position. This sequence bound 50-fold better than the immunodominant gluten 
      epitope DQ2-alpha-I-gliadin, which makes it an interesting lead compound for the 
      development of blockers. For some natural HLA-DQ2 ligands, the correlation 
      between measured and predicted affinities was poorer, but notably these peptides 
      did not have optimal amino acids at all positions. Our approach represents a 
      straightforward strategy for developing high-affinity binders to HLA class II 
      molecules.
CI  - Copyright 2010 American Society for Histocompatibility and Immunogenetics. 
      Published by Elsevier Inc. All rights reserved.
FAU - Juse, Ulrike
AU  - Juse U
AD  - Centre for Immune Regulation, Institute of Immunology, Oslo University 
      Hospital-Rikshospitalet, 0027 Oslo, Norway.
FAU - van de Wal, Yvonne
AU  - van de Wal Y
FAU - Koning, Frits
AU  - Koning F
FAU - Sollid, Ludvig M
AU  - Sollid LM
FAU - Fleckenstein, Burkhard
AU  - Fleckenstein B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100206
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ2 antigen)
RN  - 0 (Ligands)
RN  - 0 (Peptide Library)
RN  - 0 (Peptides)
SB  - IM
MH  - Amino Acid Sequence
MH  - HLA-DQ Antigens/chemistry/genetics/*immunology
MH  - Humans
MH  - Ligands
MH  - Molecular Sequence Data
MH  - *Peptide Library
MH  - Peptides/immunology
MH  - Protein Binding/genetics/immunology
MH  - Spectrometry, Mass, Electrospray Ionization
EDAT- 2010/01/29 06:00
MHDA- 2010/07/10 06:00
CRDT- 2010/01/29 06:00
PHST- 2009/08/18 00:00 [received]
PHST- 2009/11/10 00:00 [revised]
PHST- 2010/01/13 00:00 [accepted]
PHST- 2010/01/29 06:00 [entrez]
PHST- 2010/01/29 06:00 [pubmed]
PHST- 2010/07/10 06:00 [medline]
AID - S0198-8859(10)00031-5 [pii]
AID - 10.1016/j.humimm.2010.01.021 [doi]
PST - ppublish
SO  - Hum Immunol. 2010 May;71(5):475-81. doi: 10.1016/j.humimm.2010.01.021. Epub 2010 
      Feb 6.