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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1992-2-19
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pubmed:abstractText |
The coreceptor hypothesis postulates that physical association of CD4 with the TCR is required for effective signaling for T cell activation. A variety of studies has suggested that the coreceptor function of CD4 allows responses to 10- to 100-fold lower levels of peptide:self MHC class II ligand. We test the hypothesis of CD4 physical association with the TCR in two different ways. First, we use a panel of soluble antibodies directed at different TCR epitopes to activate a cloned T cell line, and show that activation by antibodies directed at a particular TCR epitope can be inhibited by anti-CD4 antibodies binding to a certain CD4 epitope. These effects establish that the interaction of CD4 and the TCR occurs in a specific orientation. Second, we use the same system to provide evidence that the physical association of CD4 with the TCR is required for effective tyrosine phosphorylation of the TCR zeta-chain subunit, presumably reflecting delivery of p56lck (lck) to the TCR. Only anti-TCR antibodies that induce physical association of CD4 with the TCR as monitored by cocapping can induce efficient tyrosine-phosphorylation of the TCR zeta-chain, unless second antibodies are used to force CD4 and the TCR to associate. Furthermore, the phosphorylation of the TCR zeta-chain exactly parallesl physical association in time and drug sensitivity. We conclude from these studies that stimuli that drive physical association of CD4 and the TCR strongly favor T cell activation, supporting the coreceptor hypothesis of CD4 function.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochalasin D,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/H-2 Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class II,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Specific Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Nocodazole,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
148
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
678-88
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:1370513-Animals,
pubmed-meshheading:1370513-Antibodies, Monoclonal,
pubmed-meshheading:1370513-Antigen-Presenting Cells,
pubmed-meshheading:1370513-Antigens, CD4,
pubmed-meshheading:1370513-CD4-Positive T-Lymphocytes,
pubmed-meshheading:1370513-Clone Cells,
pubmed-meshheading:1370513-Cross-Linking Reagents,
pubmed-meshheading:1370513-Cytochalasin D,
pubmed-meshheading:1370513-Epitopes,
pubmed-meshheading:1370513-H-2 Antigens,
pubmed-meshheading:1370513-Histocompatibility Antigens Class II,
pubmed-meshheading:1370513-Lymphocyte Activation,
pubmed-meshheading:1370513-Lymphocyte Specific Protein Tyrosine Kinase p56(lck),
pubmed-meshheading:1370513-Macromolecular Substances,
pubmed-meshheading:1370513-Mice,
pubmed-meshheading:1370513-Nocodazole,
pubmed-meshheading:1370513-Phosphotyrosine,
pubmed-meshheading:1370513-Protein-Tyrosine Kinases,
pubmed-meshheading:1370513-Receptor Aggregation,
pubmed-meshheading:1370513-Receptors, Antigen, T-Cell,
pubmed-meshheading:1370513-Tyrosine
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pubmed:year |
1992
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pubmed:articleTitle |
Physical association of CD4 with the T cell receptor.
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pubmed:affiliation |
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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