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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2004-9-15
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pubmed:databankReference |
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pubmed:abstractText |
Although non-obese diabetic (NOD) mice spontaneously develop T cell autoimmunity, it is not clear whether this phenomenon results from a defect in tolerance to self-Ag. Furthermore, as autoimmunity has been postulated to result from T cell responses directed toward self-peptides that bind with low affinity to NOD I-A(g7) MHC class II molecules, it is important to determine whether the expression of such peptides induces tolerance. We have constructed NOD transgenic (Tg) mice expressing the Leishmania antigen receptor for C kinase (LACK) Ag in either the thymus or pancreatic beta cells. We identified LACK peptides that were the targets of T cells in LACK-immunized NOD mice while binding to I-A(g7) with low affinity. While CD4(+) T cells from NOD mice secreted IFN-gamma, IL-4, IL-5 and IL-10 in response to LACK, those from LACK-expressing Tg mice secreted reduced levels of cytokines. Experiments using peptide/MHC multimers showed that LACK-expressing Tg mice exhibited self-reactive CD4(+) T cells with impaired proliferation capabilities. Hence, even self-peptides that bind to I-A(g7) with low affinity can induce tolerance in NOD mice. This result is important in light of the commonly held hypothesis that T cells reacting to peptides that bind to MHC with low affinity escape tolerance induction and cause autoimmunity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0014-2980
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pubmed:author |
pubmed-author:AppelHeinerH,
pubmed-author:BeaudoinLucieL,
pubmed-author:CazarethJulieJ,
pubmed-author:FerlinWalter GWG,
pubmed-author:GlaichenhausNicolasN,
pubmed-author:HuguesStéphanieS,
pubmed-author:JangMei-HueiMH,
pubmed-author:LehuenAgnèsA,
pubmed-author:MougneauEvelyneE,
pubmed-author:SchrickeCorinneC,
pubmed-author:WucherpfennigKai WKW
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pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2656-63
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15368281-Amino Acid Sequence,
pubmed-meshheading:15368281-Animals,
pubmed-meshheading:15368281-Antigens, Protozoan,
pubmed-meshheading:15368281-Autoantigens,
pubmed-meshheading:15368281-Cytokines,
pubmed-meshheading:15368281-Diabetes Mellitus, Type 1,
pubmed-meshheading:15368281-Female,
pubmed-meshheading:15368281-Flow Cytometry,
pubmed-meshheading:15368281-Histocompatibility Antigens Class II,
pubmed-meshheading:15368281-Immune Tolerance,
pubmed-meshheading:15368281-Mice,
pubmed-meshheading:15368281-Mice, Inbred NOD,
pubmed-meshheading:15368281-Mice, Transgenic,
pubmed-meshheading:15368281-Molecular Sequence Data,
pubmed-meshheading:15368281-Peptides,
pubmed-meshheading:15368281-Protozoan Proteins,
pubmed-meshheading:15368281-T-Lymphocytes
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pubmed:year |
2004
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pubmed:articleTitle |
Self-peptides that bind with low affinity to the diabetes-associated I-A(g7) molecule readily induce T cell tolerance in non-obese diabetic mice.
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pubmed:affiliation |
INSERM E0344, Université de Nice-Sophia Antipolis, Valbonne, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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