PMID- 11319230
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 26
DP  - 2001 Jun 29
TI  - Design, engineering, and production of human recombinant t cell receptor ligands 
      derived from human leukocyte antigen DR2.
PG  - 24170-6
AB  - Major histocompatibility complex (MHC) class II molecules are membrane-anchored 
      heterodimers on the surface of antigen-presenting cells that bind the T cell 
      receptor, initiating a cascade of interactions that results in antigen-specific 
      activation of clonal populations of T cells. Susceptibility to multiple sclerosis 
      is associated with certain MHC class II haplotypes, including human leukocyte 
      antigen (HLA) DR2. Two DRB chains, DRB5*0101 and DRB1*1501, are co-expressed in 
      the HLA-DR2 haplotype, resulting in the formation of two functional cell surface 
      heterodimers, HLA-DR2a (DRA*0101, DRB5*0101) and HLA-DR2b (DRA*0101, DRB1*1501). 
      Both isotypes can present an immunodominant peptide of myelin basic protein 
      (MBP-(84-102)) to MBP-specific T cells from multiple sclerosis patients. We have 
      previously demonstrated that the peptide binding/T cell recognition domains of 
      rat MHC class II (alpha1 and beta1 domains) could be expressed as a single exon 
      for structural and functional characterization; Burrows, G. G., Chang, J. W., 
      Bachinger, H.-P., Bourdette, D. N., Wegmann, K. W., Offner, H., and Vandenbark A. 
      A. (1999) Protein Eng. 12, 771-778; Burrows, G. G., Adlard, K. L., Bebo, B. F., 
      Jr., Chang, J. W., Tenditnyy, K., Vandenbark, A. A., and Offner, H. (2000) J. 
      Immunol. 164, 6366-6371). Single-chain human recombinant T cell receptor ligands 
      (RTLs) of approximately 200 amino acid residues derived from HLA-DR2b were 
      designed using the same principles and have been produced in Escherichia coli 
      with and without amino-terminal extensions containing antigenic peptides. 
      Structural characterization using circular dichroism predicted that these 
      molecules retained the antiparallel beta-sheet platform and antiparallel 
      alpha-helices observed in the native HLA-DR2 heterodimer. The proteins exhibited 
      a cooperative two-state thermal unfolding transition, and DR2-derived RTLs with a 
      covalently linked MBP peptide (MBP-(85-99)) showed increased stability to thermal 
      unfolding relative to the empty DR2-derived RTLs. These novel molecules represent 
      a new class of small soluble ligands for modulating the behavior of T cells and 
      provide a platform technology for developing potent and selective human 
      diagnostic and therapeutic agents for treatment of autoimmune disease.
FAU - Chang, J W
AU  - Chang JW
AD  - Department of Neurology, Shriner's Hospital for Children, and Department of 
      Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, 
      Oregon 97201, USA.
FAU - Mechling, D E
AU  - Mechling DE
FAU - Bachinger, H P
AU  - Bachinger HP
FAU - Burrows, G G
AU  - Burrows GG
LA  - eng
GR  - AI43960/AI/NIAID NIH HHS/United States
GR  - ES10554/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010423
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DR2 Antigen)
RN  - 0 (Ligands)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Peptide Fragments)
RN  - 0 (RTL303 protein, human)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Proteins)
RN  - 0 (myelin basic protein 85-99)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - HLA-DR Antigens/*chemistry/*genetics/metabolism
MH  - HLA-DR2 Antigen/chemistry/*genetics
MH  - Humans
MH  - Ligands
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Myelin Basic Protein/genetics
MH  - Peptide Fragments/genetics
MH  - Protein Engineering
MH  - Protein Structure, Secondary
MH  - Receptors, Antigen, T-Cell/*agonists
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Thermodynamics
EDAT- 2001/04/25 10:00
MHDA- 2001/08/17 10:01
CRDT- 2001/04/25 10:00
PHST- 2001/04/25 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/04/25 10:00 [entrez]
AID - S0021-9258(20)78427-9 [pii]
AID - 10.1074/jbc.M101808200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Jun 29;276(26):24170-6. doi: 10.1074/jbc.M101808200. Epub 2001 
      Apr 23.