PMID- 21469129
OWN - NLM
STAT- MEDLINE
DCOM- 20110624
LR  - 20211020
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 41
IP  - 5
DP  - 2011 May
TI  - TCR-like antibodies distinguish conformational and functional differences in two- 
      versus four-domain auto reactive MHC class II-peptide complexes.
PG  - 1465-79
LID - 10.1002/eji.201041241 [doi]
AB  - Antigen-presenting cell-associated four-domain MHC class II (MHC-II) molecules 
      play a central role in activating autoreactive CD4(+) T cells involved in 
      multiple sclerosis (MS) and type 1 diabetes (T1D). In contrast, two-domain MHC-II 
      structures with the same covalently attached self-peptide (recombinant T-cell 
      receptor ligands (RTLs)) can regulate pathogenic CD4(+) T cells and reverse 
      clinical signs of experimental autoimmune diseases. RTL1000, which is composed of 
      the beta1alpha1 domains of human leukocyte antigen (HLA)-DR2 linked to the 
      encephalitogenic human myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide, 
      was recently shown to be safe and well tolerated in a phase I clinical trial in 
      MS. To evaluate the opposing biological effects of four- versus two-domain MHC-II 
      structures, we screened phage Fab antibodies (Abs) for the neutralizing activity 
      of RTL1000. Five different TCR-like Abs were identified that could distinguish 
      between the two- versus four-domain MHC-peptide complexes while the cognate TCR 
      was unable to make such a distinction. Moreover, Fab detection of native 
      two-domain HLA-DR structures in human plasma implies that there are naturally 
      occurring regulatory MHC-peptide complexes. These results demonstrate for the 
      first time distinct conformational determinants characteristic of activating 
      versus tolerogenic MHC-peptide complexes involved in human autoimmunity.
CI  - Copyright (c) 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Dahan, Rony
AU  - Dahan R
AD  - Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
FAU - Tabul, Moran
AU  - Tabul M
FAU - Chou, Yuan K
AU  - Chou YK
FAU - Meza-Romero, Roberto
AU  - Meza-Romero R
FAU - Andrew, Shayne
AU  - Andrew S
FAU - Ferro, Adolph J
AU  - Ferro AJ
FAU - Burrows, Gregory G
AU  - Burrows GG
FAU - Offner, Halina
AU  - Offner H
FAU - Vandenbark, Arthur A
AU  - Vandenbark AA
FAU - Reiter, Yoram
AU  - Reiter Y
LA  - eng
GR  - R41 DK068881/DK/NIDDK NIH HHS/United States
GR  - NS47661/NS/NINDS NIH HHS/United States
GR  - DK068881/DK/NIDDK NIH HHS/United States
GR  - R01 AI043960-01A1/AI/NIAID NIH HHS/United States
GR  - R41 DK068881-01/DK/NIDDK NIH HHS/United States
GR  - R01 NS047661-06A1/NS/NINDS NIH HHS/United States
GR  - AI43960/AI/NIAID NIH HHS/United States
GR  - R42 DK068881/DK/NIDDK NIH HHS/United States
GR  - R42 DK068881-03/DK/NIDDK NIH HHS/United States
GR  - R01 AI043960-10/AI/NIAID NIH HHS/United States
GR  - R01 AI043960/AI/NIAID NIH HHS/United States
GR  - R01 NS047661-05/NS/NINDS NIH HHS/United States
GR  - R01 NS047661-01A2/NS/NINDS NIH HHS/United States
GR  - R01 NS047661/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110412
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Glycoproteins)
RN  - 0 (HLA-DR2 Antigen)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Peptide Fragments)
RN  - 0 (RTL1000 protein)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (myelin oligodendrocyte glycoprotein (35-55))
SB  - IM
MH  - Animals
MH  - Antigen-Presenting Cells/*immunology
MH  - Autoimmunity/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Diabetes Mellitus, Type 1/immunology
MH  - Encephalomyelitis, Autoimmune, Experimental/immunology/therapy
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Glycoproteins
MH  - HLA-DR2 Antigen/chemistry/genetics/immunology
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Humans
MH  - Immune Tolerance
MH  - Immunoglobulin Fab Fragments/immunology
MH  - Major Histocompatibility Complex/immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - Multiple Sclerosis/immunology/therapy
MH  - Myelin-Oligodendrocyte Glycoprotein
MH  - Peptide Fragments
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - Recombinant Fusion Proteins/blood/immunology
MH  - Recombinant Proteins/immunology
PMC - PMC3085348
MID - NIHMS284527
COIS- CONFLICT OF INTEREST Dr. Burrows, Dr. Offner, Dr. Vandenbark, and OHSU have a 
      significant financial interest in Artielle ImmunoTherapeutics, Inc., a company 
      that may have a commercial interest in the results of this research and 
      technology. This potential conflict of interest has been reviewed and managed by 
      the OHSU and VAMC Conflict of Interest in Research Committees. Dr. Ferro has a 
      financial interest in Artielle ImmunoTherapeutics.
EDAT- 2011/04/07 06:00
MHDA- 2011/06/28 06:00
PMCR- 2012/05/01
CRDT- 2011/04/07 06:00
PHST- 2010/11/09 00:00 [received]
PHST- 2011/01/02 00:00 [revised]
PHST- 2011/02/11 00:00 [accepted]
PHST- 2011/04/07 06:00 [entrez]
PHST- 2011/04/07 06:00 [pubmed]
PHST- 2011/06/28 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - 10.1002/eji.201041241 [doi]
PST - ppublish
SO  - Eur J Immunol. 2011 May;41(5):1465-79. doi: 10.1002/eji.201041241. Epub 2011 Apr 
      12.