PMID- 15665083
OWN - NLM
STAT- MEDLINE
DCOM- 20050328
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 102
IP  - 5
DP  - 2005 Feb 1
TI  - Peptide 15-mers of defined sequence that substitute for random amino acid 
      copolymers in amelioration of experimental autoimmune encephalomyelitis.
PG  - 1620-5
AB  - Myelin basic protein (MBP) is a major candidate autoantigen in multiple sclerosis 
      (MS). Its immunodominant epitope, MBP 85-99, forms a complex with human leukocyte 
      antigen (HLA)-DR2 with which multiple sclerosis is genetically associated. 
      Copolymer 1 (Copaxone), a random amino acid copolymer [poly (Y,E,A,K)n] as well 
      as two modified synthetic copolymers [poly (F,Y,A,K)n and poly (V,W,A,K)n] also 
      form complexes with HLA-DR2 (DRA/DRB1*1501) and compete with MBP 85-99 for 
      binding. Moreover, two high-affinity synthetic peptide 15-mers that could inhibit 
      binding even more effectively were previously designed. Here, we show that 
      further-modified peptide 15-mers inhibited even more strongly (in order J5 > J3 > 
      J2) both the binding of MBP 85-99 to HLA-DR2 and IL-2 production by two MBP 
      85-99-specific HLA-DR2-restricted T cells. J5, J3, and J2 also suppressed both 
      MBP 85-99-induced experimental autoimmune encephalomyelitis (EAE) in humanized 
      mice and proteolipid protein 139-151-induced EAE in SJL/J mice. Moreover, none of 
      these previously uncharacterized peptide inhibitors crossreacted with MBP 85-99- 
      or proteolipid protein 139-151-specific T cells. In both cases, spleen and lymph 
      node cultures stimulated with these peptides produced large amounts of Th2 
      cytokines (IL-4 and IL-10), and adoptive transfer of established T cell lines 
      suppressed disease induction. These peptide 15-mers provide specific, nonrandom 
      sequences that appear to be at least as effective as random copolymers in 
      suppressing EAE in several models.
FAU - Stern, Joel N H
AU  - Stern JN
AD  - Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 
      02138, USA.
FAU - Illes, Zsolt
AU  - Illes Z
FAU - Reddy, Jayagopala
AU  - Reddy J
FAU - Keskin, Derin B
AU  - Keskin DB
FAU - Fridkis-Hareli, Masha
AU  - Fridkis-Hareli M
FAU - Kuchroo, Vijay K
AU  - Kuchroo VK
FAU - Strominger, Jack L
AU  - Strominger JL
LA  - eng
GR  - R01 NS030843/NS/NINDS NIH HHS/United States
GR  - R01 AI 49524/AI/NIAID NIH HHS/United States
GR  - R01 AI049524/AI/NIAID NIH HHS/United States
GR  - R01 NS30843/NS/NINDS NIH HHS/United States
GR  - R01 NS38037/NS/NINDS NIH HHS/United States
GR  - P01 NS038037/NS/NINDS 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 - 20050121
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Peptides)
SB  - IM
MH  - Adoptive Transfer
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Drug Design
MH  - Encephalomyelitis, Autoimmune, Experimental/*drug therapy/immunology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Peptides/chemical synthesis/chemistry/*pharmacology/*therapeutic use
MH  - T-Lymphocytes/drug effects/immunology
PMC - PMC547868
EDAT- 2005/01/25 09:00
MHDA- 2005/03/29 09:00
PMCR- 2005/08/01
CRDT- 2005/01/25 09:00
PHST- 2005/01/25 09:00 [pubmed]
PHST- 2005/03/29 09:00 [medline]
PHST- 2005/01/25 09:00 [entrez]
PHST- 2005/08/01 00:00 [pmc-release]
AID - 0409022102 [pii]
AID - 01021620 [pii]
AID - 10.1073/pnas.0409022102 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1620-5. doi: 10.1073/pnas.0409022102. 
      Epub 2005 Jan 21.