Document Detail

Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling.
MedLine Citation:
PMID:  14586424     Owner:  NLM     Status:  MEDLINE    
Lymphocyte antigen receptors are responsible for inducing the opposite responses of immunity or tolerance. How the correct polarity of antigen receptor signaling is encoded has been an enduring enigma. Here we summarize recent advances defining key scaffolding molecules, CARMA1 (also known as CARD11) and the Cbl family of ubiquitin ligases, required for either immunogenic or tolerogenic signaling by antigen receptors. These scaffolding proteins may determine the polarity of response to antigen by promoting assembly around antigen receptors of competing multiprotein signal complexes: immunosomes versus tolerosomes. Each of the factors that influence immunogenicity or tolerogenicity--stage of lymphocyte differentiation, concurrent engagement of inhibitory or costimulatory receptors, extent of receptor crosslinking, and prior antigen experience--may be integrated in lymphocytes through their capacity to influence the probability of assembling immunosomes versus tolerosomes.
Jesse E Jun; Christopher C Goodnow
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Nature immunology     Volume:  4     ISSN:  1529-2908     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-30     Completed Date:  2003-11-25     Revised Date:  2007-11-08    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1057-64     Citation Subset:  IM    
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia.
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MeSH Terms
Antibodies / immunology*
Apoptosis Regulatory Proteins
CARD Signaling Adaptor Proteins
Calcium Signaling / physiology
Guanylate Cyclase / metabolism
Immune Tolerance / immunology*
Membrane Proteins / metabolism
NF-kappa B / metabolism
Receptors, Antigen / immunology*
Ubiquitin-Protein Ligases / metabolism
Reg. No./Substance:
0/Antibodies; 0/Apoptosis Regulatory Proteins; 0/CARD Signaling Adaptor Proteins; 0/Membrane Proteins; 0/NF-kappa B; 0/Receptors, Antigen; EC protein, human; EC Cyclase; EC Ligases

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