Source:http://linkedlifedata.com/resource/pubmed/id/10744652
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2000-7-25
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| pubmed:abstractText |
Campath-1H, a humanized mAb undergoing clinical trials for treatment of leukemia, transplantation and autoimmune diseases, produces substantial lymphocyte depletion in vivo. The antibody binds to CD52, a highly glycosylated molecule attached to the membrane by a glycosylphosphatidylinositol anchor. Cross-linked Campath-1H is known to activate T cells in vitro. We have investigated the molecular basis for these effects by comparing the protein tyrosine phosphorylation signals induced by Campath-1H and the CD3 mAb OKT3 in primary T cells, and in CD45(+)TCR(+), CD45(-)TCR(+) and CD45(+)TCR(-) Jurkat subclones transfected with CD52. Our results show that Campath-1H triggers similar tyrosine phosphorylation events as OKT3 in both primary T cells and in the CD45(+)TCR(+) Jurkat sub-clone, albeit at quantitatively lower levels. However, no phospholipase C gamma 1 activation nor calcium signals were detected in response to CD52 ligation. The CD52-mediated induction of protein tyrosine phosphorylation was absolutely dependent upon the expression of both the TCR and the CD45 phosphotyrosine phosphatase at the cell surface. Cross-linking of Campath-1H was essential for signal transduction in all cells investigated. Fluorescence resonance energy transfer was used to demonstrate CD52 homo-association at the cell surface in Jurkat T cells in a TCR- and CD45-independent manner, and CD52-TCR association in CD45(+)TCR(+) cells. We propose a model to explain the activating effects of Campath-1H in which CD52 mAb cross-linking causes the trapping of TCR polypeptides within molecular complexes at the cell surface, thereby inducing signals via the TCR by a process which depends on the CD45-mediated regulation of the p56(lck) and p59(fyn) tyrosine kinases.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, Humanized,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD45,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/CD52 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/alemtuzumab
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0953-8178
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
12
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
505-16
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10744652-Antibodies, Monoclonal,
pubmed-meshheading:10744652-Antibodies, Monoclonal, Humanized,
pubmed-meshheading:10744652-Antibodies, Neoplasm,
pubmed-meshheading:10744652-Antigens, CD,
pubmed-meshheading:10744652-Antigens, CD45,
pubmed-meshheading:10744652-Antigens, Neoplasm,
pubmed-meshheading:10744652-Calcium,
pubmed-meshheading:10744652-Calcium Signaling,
pubmed-meshheading:10744652-Cells, Cultured,
pubmed-meshheading:10744652-Glycoproteins,
pubmed-meshheading:10744652-Humans,
pubmed-meshheading:10744652-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:10744652-Isoenzymes,
pubmed-meshheading:10744652-Jurkat Cells,
pubmed-meshheading:10744652-Phospholipase C gamma,
pubmed-meshheading:10744652-Receptors, Antigen, T-Cell,
pubmed-meshheading:10744652-Signal Transduction,
pubmed-meshheading:10744652-T-Lymphocytes,
pubmed-meshheading:10744652-Transfection,
pubmed-meshheading:10744652-Type C Phospholipases
|
| pubmed:year |
2000
|
| pubmed:articleTitle |
The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells.
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| pubmed:affiliation |
Laboratory of Lymphocyte Signalling and Development, Molecular Immunology Programme, The Babraham Institute, Cambridge CB2 4AT, UK.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|