Journal
JOURNAL OF IMMUNOLOGY
Volume 189, Issue 10, Pages 4728-4739Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1201507
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Funding
- National Center for Research Resources Grant [2P20RR017670-06 Project 5, 2P20RR017670, P20RR015583]
- University of Montana University Grant Program [MRA 380, MRA 404]
- University of Montana Fluorescence Cytometry
- Molecular Histology and Fluorescence Imaging core facilities
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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. The Journal of Immunology, 2012, 189: 4728-4739.
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