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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1994-3-9
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pubmed:abstractText |
Interactions of interleukin-2 (IL-2) with its high-affinity, heterotrimeric receptor (IL-2R alpha beta gamma) play a pivotal role in the autocrine pathway of T lymphocyte expansion required in an immune response. Mutations in the IL-2R gamma chain-encoding gene have been found in SCIDX1, a primary immunodeficiency characterized by the absence of T cell and NK cell development. We have investigated six unrelated SCIDX1 patients for molecular abnormalities of the IL-2R gamma gene. A variety of defects were identified, including the absence of transcripts, frame-shift deletions and point mutations within canonical cytokine receptor motifs (conserved cysteines and the "WS" box). The ability of these mutated IL-2R gamma chains to participate in the function of a high-affinity IL-2R complex was examined by radiolabeled IL-2 binding studies using Epstein-Barr virus-transformed B lymphoblastoid cell lines (B-LCL) derived from SCIDX1 patients. Although normal control B-LCL express high-affinity IL-2 binding sites (Kd = 60 pM, 150 sites/cell), B-LCL derived from SCIDX1 patients failed to bind IL-2 under high-affinity conditions. These SCIDX1 mutations confirm the critical role of the IL-2R gamma chain in T cell and NK cell development. In addition, these data provide insight into the structure/function relationship of the IL-2R gamma chain by identifying residues required for the formation of a high-affinity IL-2R complex.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0014-2980
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
24
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pubmed:geneSymbol |
IL-2R&ggr;
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
475-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8299698-Base Sequence,
pubmed-meshheading:8299698-DNA Primers,
pubmed-meshheading:8299698-Humans,
pubmed-meshheading:8299698-Molecular Sequence Data,
pubmed-meshheading:8299698-Point Mutation,
pubmed-meshheading:8299698-RNA, Messenger,
pubmed-meshheading:8299698-Receptors, Interleukin-2,
pubmed-meshheading:8299698-Severe Combined Immunodeficiency,
pubmed-meshheading:8299698-X Chromosome
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pubmed:year |
1994
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pubmed:articleTitle |
Interleukin-2 (IL-2) receptor gamma chain mutations in X-linked severe combined immunodeficiency disease result in the loss of high-affinity IL-2 receptor binding.
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pubmed:affiliation |
INSERM U132, Hôpital Necker-Enfants Malades, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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