Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells

Baoli Yang; Denise L Gay; Megan K.L MacLeod; Xiao Cao; Tamara Hala; Eileen M Sweezer; John Kappler; Philippa Marrack; Paula M Oliver

doi:10.1038/ni.1670

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Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells

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Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells

Baoli Yang, Denise L Gay, Megan K.L MacLeod, Xiao Cao, Tamara Hala, Eileen M Sweezer, John Kappler, Philippa Marrack and Paula M Oliver

Nature immunology, Vol.9(12), pp.1356-1363

12/2008

DOI: 10.1038/ni.1670

PMCID: PMC2935464

PMID: 18931680

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Abstract

Nedd4 and Itch are E3 ubiquitin ligases that, in vitro , ubiquitinate similar targets and thus are thought to function similarly. T cells lacking Itch show spontaneous activation and T helper type 2 (T H 2) polarization. To test whether the loss of Nedd4 affects T cells in the same way, we generated Nedd4 +/+ and Nedd4 −/− fetal liver chimeras. Nedd4 −/− T cells developed normally but proliferated less, produced less interleukin 2, and provided inadequate help to B cells. Nedd4 −/− T cells contain increased amounts of Cbl-b protein, and Nedd4 was required for Cbl-b poly-ubquitination induced by CD28 co-stimulation. These data demonstrate that Nedd4 promotes the conversion of naive T cells into activated T cells. We propose that Nedd4 and Itch ubiquitinate distinct target proteins in vivo .

Details

Title: Subtitle: Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells
Creators: Baoli Yang - Department of Obstetrics & Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242 USA
Denise L Gay - Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Megan K.L MacLeod - Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO 80206 USA
Xiao Cao - Department of Obstetrics & Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242 USA
Tamara Hala - Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Eileen M Sweezer - Department of Obstetrics & Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242 USA
John Kappler - Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO 80206 USA
Philippa Marrack - Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO 80206 USA
Paula M Oliver - Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO 80206 USA
Resource Type: Journal article
Publication Details: Nature immunology, Vol.9(12), pp.1356-1363
DOI: 10.1038/ni.1670
PMID: 18931680
PMCID: PMC2935464
NLM abbreviation: Nat Immunol
ISSN: 1529-2908
eISSN: 1529-2916
Language: English
Date published: 12/2008
Academic Unit: BioVentures Center; Obstetrics and Gynecology
Record Identifier: 9984083233602771

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