Mechanisms of cellular communication through intercellular protein transfer

Abstract

In a multicellular system, cellular communication is a must for orchestration and coordination of cellular events. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the intercellular communication. An intercellular exchange of proteins or intact membrane patches is a ubiquitous phenomenon, and has been the subject of renewed interest, particularly in the context of immune cells. Recent evidence implicates that intercellular protein transfers, including trogocytosis is an important mechanism of the immune system to modulate immune responses and transferred proteins can also contribute to pathology. It has been demonstrated that intercellular protein transfer can be through the internalization/pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Exchange of membrane molecules/antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we will discuss the important findings concerning intercellular protein transfers, possible mechanisms and highlight their physiological relevance to the immune system, with special reference to T cells such as the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules.

Fig 1

Mechanism for intercellular protein transfer between immune cells and its immunological relevance. (A) Internalization and recycling pathway; (B) dissociation-associated pathway; (C) exosome uptake; (D) membrane nanotube formation. IS or tight contact between lymphocytes and their targets enables intercellular exchange of cellular proteins. Some membrane proteins are snatched by specific receptors, and other, ‘bystander ligands’ and membrane patches can also be acquired. This intercellular exchange of proteins has an important influence on the course of T-cell-mediated immune responses. (E) In some circumstances, the intercellular transfer of cell-surface proteins from APCs to T cells can amplify immune responses or broaden cellular stimulation or activate neighbouring effector cells leading to augmenting cytokine production. (F) In some other conditions, the trogocytosis may induce anergy or tolerance, and T-cell function as regulatory T cells in subsequent immune modulation. In addition, the process of trogocytosis can dampen immune responses by fratricide killing, i.e. lysis of CTLs by neighbouring CTLs. (MVBs; multivesicular bodies).