Publication Date:
1995-01-27
Description:
Small changes in the peptide-major histocompatibility complex (MHC) molecule ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully activating complexes into partially activating or even inhibitory ones. This study examined early TCR-dependent signals induced by such partial agonists or antagonists. In contrast to typical agonist ligands, both an antagonist and several partial agonists stimulated a distinct pattern of zeta chain phosphorylation and failed to activate associated ZAP-70 kinase. These results identify a specific step in the early tyrosine phosphorylation cascade that is altered after TCR engagement with modified peptide-MHC molecule complexes. This finding may explain the different biological responses to TCR occupancy by these variant ligands.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Madrenas, J -- Wange, R L -- Wang, J L -- Isakov, N -- Samelson, L E -- Germain, R N -- New York, N.Y. -- Science. 1995 Jan 27;267(5197):515-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7824949" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Clone Cells
;
Cytochrome c Group/pharmacology
;
Enzyme Activation
;
Histocompatibility Antigens Class II/genetics/immunology/*pharmacology
;
Interleukin-2/biosynthesis
;
L Cells (Cell Line)
;
Ligands
;
Lymphocyte Activation
;
Membrane Proteins/*metabolism
;
Mice
;
Molecular Sequence Data
;
Mutation
;
Peptide Fragments/pharmacology
;
Phosphorylation
;
Protein-Tyrosine Kinases/*metabolism
;
Receptors, Antigen, T-Cell/agonists/antagonists & inhibitors/*metabolism
;
Signal Transduction
;
T-Lymphocytes, Helper-Inducer/*immunology
;
Tyrosine/metabolism
;
ZAP-70 Protein-Tyrosine Kinase
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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