Trogocytosis results in sustained intracellular signaling in CD4(+) T cells.
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.
Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
Douglas G
DG
Osborne
Scott A
SA
Wetzel
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D011743:Pyrimidines / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
C412373:AG 1879; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D011743:Pyrimidines; D011948:Receptors, Antigen, T-Cell; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D048052:Mitogen-Activated Protein Kinase 3