Cutting edge

Regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination

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

Research output: Contribution to journalArticle

105 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2236-2240
Number of pages5
JournalJournal of Immunology
Volume169
Issue number5
Publication statusPublished - Sep 1 2002

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Ubiquitination
T-Lymphocytes
Ligases
Ubiquitin

ASJC Scopus subject areas

  • Immunology

Cite this

Cutting edge : Regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. / Zhang, Jian; Bárdos, T.; Li, Dongdong; Gál, István; Vermes, C.; Xu, Jianye; Mikecz, Katalin; Finnegan, Alison; Lipkowitz, Stan; Glant, Tibor T.

In: Journal of Immunology, Vol. 169, No. 5, 01.09.2002, p. 2236-2240.

Research output: Contribution to journalArticle

Zhang, J, Bárdos, T, Li, D, Gál, I, Vermes, C, Xu, J, Mikecz, K, Finnegan, A, Lipkowitz, S & Glant, TT 2002, 'Cutting edge: Regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination', Journal of Immunology, vol. 169, no. 5, pp. 2236-2240.
Zhang, Jian ; Bárdos, T. ; Li, Dongdong ; Gál, István ; Vermes, C. ; Xu, Jianye ; Mikecz, Katalin ; Finnegan, Alison ; Lipkowitz, Stan ; Glant, Tibor T. / Cutting edge : Regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. In: Journal of Immunology. 2002 ; Vol. 169, No. 5. pp. 2236-2240.
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