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J Immunol. 2012 Nov 15;189(10):4728-39. doi: 10.4049/jimmunol.1201507. Epub 2012 Oct 12.

Trogocytosis results in sustained intracellular signaling in CD4(+) T cells.

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1
Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.

Abstract

CD4(+) T cells capture membrane and membrane-bound molecules from APCs directly from the immunological synapse in a process termed trogocytosis. The function and biological consequences of trogocytosis are largely unknown. In this study, we examine the biological significance of this phenomenon on the trogocytosis-positive T cell. We used murine fibroblasts expressing GFP-tagged I-E(k) molecules loaded with a covalently attached antigenic peptide (moth cytochrome c 88-103) to present Ag to primary TCR transgenic T cells. Using a combination of high-resolution light microscopy and flow cytometry, we show that the trogocytosed molecules are retained on the surface of the T cell in association with the TCR and elevated phosphorylated ZAP-70, phosphorylated tyrosine, and phosphorylated ERK 1/2. Through the use of the Src inhibitor PP2, we demonstrate that trogocytosed molecules directly sustain TCR signaling. In addition, after removal of APC, trogocytosis-positive cells preferentially survive in culture over several days. These novel findings suggest that trogocytosed molecules continue to engage their receptors on the T cell surface and sustain intracellular signaling leading to selective survival of these cells.

PMID:
23066151
DOI:
10.4049/jimmunol.1201507
[Indexed for MEDLINE]
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