TY - JOUR
T1 - Trogocytosis results in sustained intracellular signaling in CD4 + T cells
AU - Osborne, Douglas G.
AU - Wetzel, Scott A.
PY - 2012/11/15
Y1 - 2012/11/15
N2 - 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-Ek 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.
AB - 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-Ek 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.
UR - http://www.scopus.com/inward/record.url?scp=84868543217&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1201507
DO - 10.4049/jimmunol.1201507
M3 - Article
C2 - 23066151
AN - SCOPUS:84868543217
SN - 0022-1767
VL - 189
SP - 4728
EP - 4739
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -