Wide-Scale Quantitative Phosphoproteomic Analysis Reveals That Cold Treatment of T Cells Closely Mimics Soluble Antibody Stimulation

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.