PMID- 21299528
OWN - NLM
STAT- MEDLINE
DCOM- 20110610
LR  - 20131121
IS  - 1399-0039 (Electronic)
IS  - 0001-2815 (Linking)
VI  - 77
IP  - 3
DP  - 2011 Mar
TI  - The HLA-DP2 protein binds the immunodominant epitope from myelin basic protein, 
      MBP85-99, with high affinity.
PG  - 229-34
LID - 10.1111/j.1399-0039.2010.01614.x [doi]
AB  - Myelin basic protein (MBP) is a candidate autoantigen in multiple sclerosis (MS). 
      The immunodominant epitope for T-cell responses is assigned to the amino acid 
      sequence MBP84-102, which binds to human leukocyte antigen (HLA)-DR2a (DRB5*0101) 
      and HLA-DR2b (DRB1*1501) of the HLA-DR2 haplotype carrying the strongest genetic 
      association with MS. In contrast with HLA-DR and -DQ molecules, HLA-DP molecules 
      are poorly characterized with respect to the binding of self-peptides. We show 
      here that HLA-DP2 binds MBP85-99 with high affinity, and that the amino acid 
      residues in position MBP91, MBP92 and MBP93 are influencing the binding, as shown 
      by alanine scans. We further used a series of truncated peptides to identify the 
      core of the binding. Moving the frame along the peptide from residues 87-97 to 
      89-99 progressively decreased the binding affinity for HLA-DP2, while moving 
      further towards the C-terminal completely abrogated the binding of peptides to 
      HLA-DP2. The data suggest that the docking of the MBP85-99 peptide into the 
      HLA-DP2 groove is dependent on MBP88V and MBP89V and may use either of them as 
      primary anchor for the p1 position. HLA-DP2 might thus present the MBP85-99 
      peptide in the same register as the HLA-DRB1*1501, where the MBP89V is preferred 
      as the p1 anchor. Notably, full-length MBP was able to compete for peptide 
      binding with an affinity similar to that seen for the high-affinity binding 
      peptides, DRalpha170-83 and IIP53-65. In summary, the HLA-DP2 molecule binds the 
      immunodominant epitope in MS, MBP85-99, possibly in more than one register.
CI  - (c) 2011 John Wiley & Sons A/S.
FAU - Hansen, B E
AU  - Hansen BE
AD  - Department of Rheumatology, Institute for Inflammation Research, Copenhagen 
      University Hospital, Rigshospitalet, Copenhagen, Denmark. behmail@get2net.dk
FAU - Nielsen, C H
AU  - Nielsen CH
FAU - Madsen, H O
AU  - Madsen HO
FAU - Ryder, L P
AU  - Ryder LP
FAU - Jakobsen, B K
AU  - Jakobsen BK
FAU - Svejgaard, A
AU  - Svejgaard A
LA  - eng
PT  - Journal Article
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA-DP Antigens)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPw2 antigen)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
RN  - 0 (myelin basic protein 85-99)
RN  - 8PJ61P6TS3 (1-Butanol)
SB  - IM
MH  - 1-Butanol/pharmacology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cells, Cultured
MH  - Drosophila melanogaster
MH  - Enzyme-Linked Immunosorbent Assay
MH  - HLA-DP Antigens/chemistry/immunology/isolation & purification/*metabolism
MH  - HLA-DP beta-Chains
MH  - Humans
MH  - Immunodominant Epitopes/*metabolism
MH  - Multiple Sclerosis/immunology/metabolism
MH  - Myelin Basic Protein/immunology/*metabolism
MH  - Peptide Fragments/immunology/*metabolism
MH  - Protein Binding/immunology
MH  - Recombinant Proteins/immunology/metabolism
MH  - Substrate Specificity
EDAT- 2011/02/09 06:00
MHDA- 2011/06/11 06:00
CRDT- 2011/02/09 06:00
PHST- 2011/02/09 06:00 [entrez]
PHST- 2011/02/09 06:00 [pubmed]
PHST- 2011/06/11 06:00 [medline]
AID - 10.1111/j.1399-0039.2010.01614.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2011 Mar;77(3):229-34. doi: 10.1111/j.1399-0039.2010.01614.x.