title: Wide-scale quantitative phosphoproteomic analysis reveals that cold treatment of T cells closely mimics soluble antibody stimulation.
abstract: The activation of T lymphocytes through antigen-mediated T cell receptor (TCR) clustering is vital in regulating the adaptive immune response. Although T cell receptor signaling has been extensively studied, the fundamental mechanisms for signal initiation are not fully understood. Reduced temperatures have initiated some of the hallmarks of TCR signaling, such as increased phosphorylation and activation on ERK and calcium release from the endoplasmic reticulum, as well as coalesced the T cell membrane microdomains. The precise mechanism of the TCR signaling initiation due to temperature change remains obscure. One critical question is whether the signaling initiated by the cold treatment of T cells differs from the signaling initiated by the cross-linking of the T cell receptor. To address this uncertainty, we performed a wide-scale, quantitative mass-spectrometry-based phosphoproteomic analysis on T cells stimulated either by temperature shifts or through the cross-linking of the TCR. Careful statistical comparisons between the two stimulations revealed a striking level of identity among the subset of 339 sites that changed significantly with both stimulations. This study demonstrates for the first time, in unprecedented detail, that T cell cold treatment was sufficient to initiate signaling patterns that were nearly identical to those of soluble antibody stimulation, shedding new light on the mechanism of activation of these critically important immune cells.
authors.affiliation: †Department of Chemistry, Brown University, Providence, Rhode Island 02912, United States.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Ji
authors.affiliation: †Department of Chemistry, Brown University, Providence, Rhode Island 02912, United States.|‡Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02903, United States.
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Salomon
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D000906:Antibodies / Q000494:pharmacology; D003080:Cold Temperature; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D021962:Membrane Microdomains / Q000187:drug effects / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology / Q000302:isolation & purification*; D010766:Phosphorylation; D020543:Proteome / Q000276:immunology / Q000302:isolation & purification*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D020543:Proteome; D011948:Receptors, Antigen, T-Cell
keywords: Jurkat; T cell signaling; cold stimulation; immunology; mass spectrometry; phosphoproteome
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