PMID- 16079912
OWN - NLM
STAT- MEDLINE
DCOM- 20051025
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 24
IP  - 17
DP  - 2005 Sep 7
TI  - Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide 
      and a multiple sclerosis-associated MHC class II molecule.
PG  - 2968-79
AB  - Multiple sclerosis is mediated by T-cell responses to central nervous system 
      antigens such as myelin basic protein (MBP). To investigate self-peptide/major 
      histocompatibility complex (MHC) recognition and T-cell receptor (TCR) 
      degeneracy, we determined the crystal structure, at 2.8 A resolution, of an 
      autoimmune TCR (3A6) bound to an MBP self-peptide and the multiple 
      sclerosis-associated MHC class II molecule, human leukocyte antigen (HLA)-DR2a. 
      The complex reveals that 3A6 primarily recognizes the N-terminal portion of MBP, 
      in contrast with antimicrobial and alloreactive TCRs, which focus on the peptide 
      center. Moreover, this binding mode, which may be frequent among autoimmune TCRs, 
      is compatible with a wide range of orientation angles of TCR to peptide/MHC. The 
      interface is characterized by a scarcity of hydrogen bonds between TCR and 
      peptide, and TCR-induced conformational changes in MBP/HLA-DR2a, which likely 
      explain the low observed affinity. Degeneracy of 3A6, manifested by recognition 
      of superagonist peptides bearing substitutions at nearly all TCR-contacting 
      positions, results from the few specific interactions between 3A6 and MBP, 
      allowing optimization of interface complementarity through variations in the 
      peptide.
FAU - Li, Yili
AU  - Li Y
AD  - Center for Advanced Research in Biotechnology, WM Keck Laboratory for Structural 
      Biology, University of Maryland Biotechnology Institute, Rockville, MD 20850, 
      USA.
FAU - Huang, Yuping
AU  - Huang Y
FAU - Lue, Jessica
AU  - Lue J
FAU - Quandt, Jacqueline A
AU  - Quandt JA
FAU - Martin, Roland
AU  - Martin R
FAU - Mariuzza, Roy A
AU  - Mariuzza RA
LA  - eng
SI  - PDB/1ZGL
GR  - R01 AI036900/AI/NIAID NIH HHS/United States
GR  - R37 AI036900/AI/NIAID NIH HHS/United States
GR  - AI36900/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 - 20050804
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (HLA-DR2 Antigen)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (myelin basic protein 89-101)
SB  - IM
MH  - Autoimmunity
MH  - Dimerization
MH  - HLA-DR2 Antigen/*chemistry
MH  - Humans
MH  - Hydrogen Bonding
MH  - Models, Molecular
MH  - Multiple Sclerosis/immunology
MH  - Myelin Basic Protein/*chemistry
MH  - Peptide Fragments/*chemistry
MH  - Peptides/*chemistry
MH  - Protein Conformation
MH  - Receptors, Antigen, T-Cell/*chemistry
MH  - Surface Plasmon Resonance
PMC - PMC1201352
EDAT- 2005/08/05 09:00
MHDA- 2005/10/26 09:00
PMCR- 2005/09/07
CRDT- 2005/08/05 09:00
PHST- 2005/05/17 00:00 [received]
PHST- 2005/07/14 00:00 [accepted]
PHST- 2005/08/05 09:00 [pubmed]
PHST- 2005/10/26 09:00 [medline]
PHST- 2005/08/05 09:00 [entrez]
PHST- 2005/09/07 00:00 [pmc-release]
AID - 7600771 [pii]
AID - 10.1038/sj.emboj.7600771 [doi]
PST - ppublish
SO  - EMBO J. 2005 Sep 7;24(17):2968-79. doi: 10.1038/sj.emboj.7600771. Epub 2005 Aug 
      4.