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Article Dans Une Revue Journal of Experimental Medicine Année : 2016

The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells

Résumé

The RLTPR cytosolic protein, also known as CAR MIL2, is essential for CD28 co-stimulation in mice, but its importance in human T cells and mode of action remain elusive. Here, using affinity purification followed by mass spectrometry analysis, we showed that RLTPR acts as a scaffold, bridging CD28 to the CARD11/CARMA1 cytosolic adaptor and to the NF-kappa B signaling pathway, and identified proteins not found before within the CD28 signaling pathway. We further demonstrated that RLTPR is essential for CD28 co-stimulation in human T cells and that its noncanonical pleckstrin-homology domain, leucine-rich repeat domain, and proline-rich region were mandatory for that task. Although RLTPR is thought to function as an actin-uncapping protein, this property was dispensable for CD28 co-stimulation in both mouse and human. Our findings suggest that the scaffolding role of RLTPR predominates during CD28 co-stimulation and underpins the similar function of RLTPR in human and mouse T cells. Along that line, the lack of functional RLTPR molecules impeded the differentiation toward Th1 and Th17 fates of both human and mouse CD4(+) T cells. RLTPR was also expressed in both human and mouse B cells. In the mouse, RLTPR did not play, however, any detectable role in BCR-mediated signaling and T cell-independent B cell responses.

Dates et versions

hal-01455791 , version 1 (03-02-2017)

Identifiants

Citer

Romain Roncagalli, Margot Cucchetti, Nicolas Jarmuzynski, Claude Grégoire, Elise Bergot, et al.. The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells. Journal of Experimental Medicine, 2016, 213 (11), pp.2437-2457. ⟨10.1084/jem.20160579⟩. ⟨hal-01455791⟩
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