Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination

Jian Zhang; Tamás Bárdos; Dongdong Li; István Gál; Csaba Vermes; Jianye Xu; Katalin Mikecz; Alison Finnegan; Stan Lipkowitz; Tibor T Glant

doi:10.4049/jimmunol.169.5.2236

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Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination

Journal article

Peer reviewed

Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination

Jian Zhang, Tamás Bárdos, Dongdong Li, István Gál, Csaba Vermes, Jianye Xu, Katalin Mikecz, Alison Finnegan, Stan Lipkowitz and Tibor T Glant

The Journal of immunology (1950), Vol.169(5), pp.2236-2240

09/01/2002

DOI: 10.4049/jimmunol.169.5.2236

PMID: 12193687

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Abstract

Optimal T cell activation requires signaling through the TCR and CD28 costimulatory receptor. CD28 costimulation is believed to set the threshold for T cell activation. Recently, Cbl-b, a ubiquitin ligase, has been shown to negatively regulate CD28-dependent T cell activation. In this report, we show that CD28 costimulation selectively induces greater ubiquitination and degradation of Cbl-b in wild-type T cells than CD3 stimulation alone, and TCR-induced Cbl-b ubiquitination and degradation are significantly reduced in CD28-deficient T cells. Stimulation of CD28-deficient T cells with higher doses of anti-CD3 results in increased ubiquitination of Cbl-b, which correlates with enhanced T cell responses. Our results demonstrate that CD28 costimulation regulates the threshold for T cell activation, at least in part, by promoting Cbl-b ubiquitination and degradation.

T-Lymphocytes - enzymology

Humans

Ubiquitin - metabolism

Phosphoproteins - metabolism

Proteasome Endopeptidase Complex

Lymphocyte Activation - immunology

CD28 Antigens - genetics

T-Lymphocytes - metabolism

Proto-Oncogene Proteins c-cbl

Female

Phosphoproteins - physiology

Peptide Hydrolases - metabolism

CD28 Antigens - physiology

Carrier Proteins - physiology

Jurkat Cells

Cells, Cultured

Ligases - metabolism

Mice, Knockout

Ubiquitin-Protein Ligases

Adaptor Proteins, Signal Transducing

Animals

Carrier Proteins - metabolism

T-Lymphocytes - immunology

Ligases - physiology

Mice

Mice, Inbred BALB C

Details

Title: Subtitle: Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination
Creators: Jian Zhang - Section of Molecular Medicine, Department of Orthopedic Surgery, Rush Medical College at Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. jzhang1@rush.edu
Tamás Bárdos
Dongdong Li
István Gál
Csaba Vermes
Jianye Xu
Katalin Mikecz
Alison Finnegan
Stan Lipkowitz
Tibor T Glant
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.169(5), pp.2236-2240
DOI: 10.4049/jimmunol.169.5.2236
PMID: 12193687
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AR47412 / NIAMS NIH HHS AR45652 / NIAMS NIH HHS AR40310 / NIAMS NIH HHS
Language: English
Date published: 09/01/2002
Academic Unit: Pathology
Record Identifier: 9984047856202771

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