Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling

Jesse E. Jun; Christopher C. Goodnow

doi:10.1038/ni1001

Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling

Jesse E. Jun, Christopher C. Goodnow^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

87 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1057-1064
Number of pages	8
Journal	Nature Immunology
Volume	4
Issue number	11
DOIs	https://doi.org/10.1038/ni1001
Publication status	Published - Nov 2003

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abstract = "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.",

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AB - 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.

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JO - Nature Immunology

JF - Nature Immunology

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Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling

Abstract

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