ICAM-1 depletion in the center of immunological synapses is important for calcium releasing in T-cells

Yuanzhen Suo,Guosheng Jiang,Xunbin Wei,Lizeng Qin,Wei Lin,Yiwei Chu,Yuting Deng,Zhichao Fan

doi:10.1142/s1793545817500158

Abstract

T-cell activation requires the formation of the immunological synapse (IS) between a T-cell and an antigen-presenting cell (APC) to control the development of the adaptive immune response. However, calcium release, an initial signal of T-cell activation, has been found to occur before IS formation. The mechanism for triggering the calcium signaling and relationship between calcium release and IS formation remains unclear. Herein, using live-cell imaging, we found that intercellular adhesion molecule 1 (ICAM-1), an essential molecule for IS formation, accumulated and then was depleted at the center of the synapse before complete IS formation. During the process of ICAM-1 depletion, calcium was released. If ICAM-1 failed to be depleted from the center of the synapse, the sustained calcium signaling could not be induced. Moreover, depletion of ICAM-1 in ISs preferentially occurred with the contact of antigen-specific T-cells and dendritic cells (DCs). Blocking the binding of ICAM-1 and lymphocyte function-associated antigen 1 (LFA-1), ICAM-1 failed to deplete at the center of the synapse, and calcium release in T-cells decreased. In studying the mechanism of how the depletion of ICAM-1 could influence calcium release in T-cells, we found that the movement of ICAM-1 was associated with the localization of LFA-1 in the IS, which affected the localization of calcium microdomains, ORAI1 and mitochondria in IS. Therefore, the depletion of ICAM-1 in the center of the synapse is an important factor for an initial sustained calcium release in T-cells.

Highlights

The formation of the immunological synapse (IS) is a dynamic process in which a multi-molecular assembly of receptors and adhesion molecules accumulates at the interface of T-cell and antigenpresenting cells (APCs)
Here, we dynamically imaged the contact of T-cells and DC2.4-ICAM-1-EGFP cells to analyze the relationship between the movement of ICAM-1 and calcium release in T-cells
We found out that within therst 5 min of the formation of a bullseye IS, ICAM-1 accumulated at the center of the T-DC contact area, while TCR clusters moved to the interface of ICAM-1 clusters

Summary

Introduction

The formation of the immunological synapse (IS) is a dynamic process in which a multi-molecular assembly of receptors and adhesion molecules accumulates at the interface of T-cell and antigenpresenting cells (APCs) It plays a vital role in controlling T-cell activation.[1] When a T-cell recognizes the articial planar bilayer anchored with major histocompatibility complex-peptide (MHC-peptide) and intercellular adhesion molecule 1(ICAM-1),[1] a broad central zone of ICAM-1 accumulation isrstly established in the IS. ICAM-1 moves from the center to the periphery of the IS to form a ring around the TCRpMHC.[1] This classical matured IS is called a bullseye IS.[1,2] Another type of matured IS is the multifocal IS, which is characterized by interspersed ICAM-1 molecules among multiple small accumulations of TCR-pMHC complexes and phosphorylated signaling molecules at the T-DC interface.[3,4] The process of both types of synapses is characterized by ICAM-1 accumulation and exclusion from the center to the periphery of the synapse. The mechanism of how synapses control T-cell activation is still unknown

Methods

Results

Conclusion