PMID- 10689117
OWN - NLM
STAT- MEDLINE
DCOM- 20000327
LR  - 20190905
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 61
IP  - 3
DP  - 2000 Mar
TI  - Complementation between specific HLA-DR and HLA-DQ genes in transgenic mice 
      determines susceptibility to experimental autoimmune encephalomyelitis.
PG  - 279-89
AB  - To investigate the contribution of human leukocyte antigen (HLA) class II 
      molecules in susceptibility to inflammatory demyelination, we induced 
      experimental autoimmune encephalomyelitis (EAE) in transgenic (tg) mice 
      expressing the HLA-DR3, HLA-DQ8 and HLA-DQ6 molecules in the absence of 
      endogenous class II (Ab(o)). Following immunization with mouse myelin, HLA-DR3 tg 
      mice mounted strong T-cell proliferative responses, and developed inflammatory 
      lesions and demyelination in the central nervous system with mild to moderate 
      clinical symptoms of EAE. HLA-DQ8 and HLA-DQ6 tg mice elicited weak T-cell 
      proliferative responses and did not develop clinical symptoms of EAE. HLA-DR3/DQ6 
      double tg mice immunized with mouse myelin experienced clinical disease similar 
      to the single tg HLA-DR3 tg mice, indicating that expression of DQ6 in this line 
      had no effect on disease. In contrast, HLA-DR3/DQ8 double tg mice developed 
      severe inflammatory lesions and clinical disease in response to immunization with 
      mouse myelin. Our data suggest that in the presence of two susceptible class II 
      alleles, namely HLA-DR3 and DQ8, there is additional selection and expansion of 
      potential autoreactive T cells, resulting in enhanced severity of disease.
FAU - Das, P
AU  - Das P
AD  - Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
FAU - Drescher, K M
AU  - Drescher KM
FAU - Geluk, A
AU  - Geluk A
FAU - Bradley, D S
AU  - Bradley DS
FAU - Rodriguez, M
AU  - Rodriguez M
FAU - David, C S
AU  - David CS
LA  - eng
GR  - AI14764/AI/NIAID NIH HHS/United States
GR  - CA24473/CA/NCI NIH HHS/United States
GR  - NS24180/NS/NINDS NIH HHS/United States
GR  - etc.
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  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Cytokines)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ6 antigen)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Animals
MH  - Central Nervous System/pathology
MH  - Cytokines/biosynthesis
MH  - Encephalomyelitis, Autoimmune, Experimental/etiology/*genetics/pathology
MH  - *Genes, MHC Class II
MH  - *Genetic Predisposition to Disease
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DR3 Antigen/*genetics
MH  - Humans
MH  - Lymph Nodes/cytology/immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - Multiple Sclerosis/etiology/genetics
MH  - Myelin Basic Protein/immunology
MH  - Myelin Sheath/immunology
MH  - Peptide Fragments/immunology
MH  - T-Lymphocytes/immunology
EDAT- 2000/02/26 09:00
MHDA- 2000/04/01 09:00
CRDT- 2000/02/26 09:00
PHST- 2000/02/26 09:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 2000/02/26 09:00 [entrez]
AID - S0198-8859(99)00135-4 [pii]
AID - 10.1016/s0198-8859(99)00135-4 [doi]
PST - ppublish
SO  - Hum Immunol. 2000 Mar;61(3):279-89. doi: 10.1016/s0198-8859(99)00135-4.