PMID- 11937578
OWN - NLM
STAT- MEDLINE
DCOM- 20020523
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 168
IP  - 8
DP  - 2002 Apr 15
TI  - De novo central nervous system processing of myelin antigen is required for the 
      initiation of experimental autoimmune encephalomyelitis.
PG  - 4173-83
AB  - We demonstrate the absolute requirement for a functioning class II-restricted Ag 
      processing pathway in the CNS for the initiation of experimental autoimmune 
      encephalomyelitis (EAE). C57BL/6 (B6) mice deficient for the class II 
      transactivator, which have defects in MHC class II, invariant chain (Ii), and 
      H-2M (DM) expression, are resistant to initiation of myelin oligodendrocyte 
      protein (MOG) peptide, MOG(35-55)-specific EAE by both priming and adoptive 
      transfer of encephalitogenic T cells. However, class II transactivator-deficient 
      mice can prime a suboptimal myelin-specific CD4(+) Th1 response. Further, B6 mice 
      individually deficient for Ii and DM are also resistant to initiation of both 
      active and adoptive EAE. Although both Ii-deficient and DM-deficient APCs can 
      present MOG peptide to CD4(+) T cells, neither is capable of processing and 
      presenting the encephalitogenic peptide of intact MOG protein. This phenotype is 
      not Ag-specific, as DM- and Ii-deficient mice are also resistant to initiation of 
      EAE by proteolipid protein peptide PLP(178-191). Remarkably, DM-deficient mice 
      can prime a potent peripheral Th1 response to MOG(35-55), comparable to the 
      response seen in wild-type mice, yet maintain resistance to EAE initiation. Most 
      striking is the demonstration that T cells from MOG(35-55)-primed DM knockout 
      mice can adoptively transfer EAE to wild-type, but not DM-deficient, mice. 
      Together, these data demonstrate that the inability to process antigenic peptide 
      from intact myelin protein results in resistance to EAE and that de novo 
      processing and presentation of myelin Ags in the CNS is absolutely required for 
      the initiation of autoimmune demyelinating disease.
FAU - Tompkins, Stephen Mark
AU  - Tompkins SM
AD  - Department of Microbiology-Immunology and Pathology, Northwestern University 
      Medical School, Chicago, IL 60611, USA.
FAU - Padilla, Josette
AU  - Padilla J
FAU - Dal Canto, Mauro C
AU  - Dal Canto MC
FAU - Ting, Jenny P-Y
AU  - Ting JP
FAU - Van Kaer, Luc
AU  - Van Kaer L
FAU - Miller, Stephen D
AU  - Miller SD
LA  - eng
GR  - NS26543/NS/NINDS NIH HHS/United States
GR  - NS30871/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.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, Differentiation, B-Lymphocyte)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Glycoproteins)
RN  - 0 (H2-M antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Myelin Proteolipid Protein)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Trans-Activators)
RN  - 0 (invariant chain)
RN  - 0 (myelin oligodendrocyte glycoprotein (35-55))
RN  - 172228-98-7 (myelin proteolipid protein (178-191))
SB  - IM
MH  - Adoptive Transfer
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Antigen Presentation/genetics
MH  - Antigens, Differentiation, B-Lymphocyte/genetics
MH  - Cell Movement/genetics/immunology
MH  - Central Nervous System/*immunology/metabolism/pathology
MH  - Encephalomyelitis, Autoimmune, 
      Experimental/*etiology/genetics/*immunology/pathology
MH  - Epitopes, T-Lymphocyte/administration & dosage/immunology/metabolism
MH  - Female
MH  - Glycoproteins/administration & dosage/*immunology/metabolism
MH  - Histocompatibility Antigens Class II/genetics
MH  - Immunity, Innate/genetics
MH  - Injections, Subcutaneous
MH  - Lymphocyte Activation/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Myelin Proteolipid Protein/administration & dosage/immunology/metabolism
MH  - Myelin-Oligodendrocyte Glycoprotein
MH  - *Nuclear Proteins
MH  - Peptide Fragments/administration & dosage/*immunology/metabolism
MH  - Th1 Cells/immunology/metabolism
MH  - Trans-Activators/deficiency/genetics
EDAT- 2002/04/09 10:00
MHDA- 2002/05/25 10:01
CRDT- 2002/04/09 10:00
PHST- 2002/04/09 10:00 [pubmed]
PHST- 2002/05/25 10:01 [medline]
PHST- 2002/04/09 10:00 [entrez]
AID - 10.4049/jimmunol.168.8.4173 [doi]
PST - ppublish
SO  - J Immunol. 2002 Apr 15;168(8):4173-83. doi: 10.4049/jimmunol.168.8.4173.