The Role of Trogocytosis in the Modulation of Immune Cell Functions

Abstract

Trogocytosis is an active process, in which one cell extracts the cell fragment from another cell, leading to the transfer of cell surface molecules, together with membrane fragments. Recent reports have revealed that trogocytosis can modulate various biological responses, including adaptive and innate immune responses and homeostatic responses. Trogocytosis is evolutionally conserved from protozoan parasites to eukaryotic cells. In some cases, trogocytosis results in cell death, which is utilized as a mechanism for antibody-dependent cytotoxicity (ADCC). In other cases, trogocytosis-mediated intercellular protein transfer leads to both the acquisition of novel functions in recipient cells and the loss of cellular functions in donor cells. Trogocytosis in immune cells is typically mediated by receptor-ligand interactions, including TCR-MHC interactions and Fcγ receptor-antibody-bound molecule interactions. Additionally, trogocytosis mediates the transfer of MHC molecules to various immune and non-immune cells, which confers antigen-presenting activity on non-professional antigen-presenting cells. In this review, we summarize the recent advances in our understanding of the role of trogocytosis in immune modulation.

Keywords: Fcγ receptor; NK receptor; T cell receptor (TCR); Th2 differentiation; antibody-dependent cellular cytotoxicity (ADCC); cross-dressing; intracellular bacteria; major histocompatibility complex (MHC); trogocytosis.

Figure 1

Characteristics of phagocytosis vs. trogocytosis. (A) In the process of phagocytosis, phagocytes swallow the whole cell body of target cells; (B) in the process of trogocytosis, recipient cells nibble the cell body of donor cells. Trogocytosis results in either (1) the death of target cells (trogocytosis-mediated cell death) or (2) the transfer of cell surface molecules, together with membrane patches, from donor cells to recipient cells (trogocytosis-mediated material transfer).

Figure 2

Trogocytosis-mediated cell death by amoebae and neutrophils. (A) Amoebae nibble human cells via trogocytosis, leading to the death of human cells. The interaction between amoebae and human cells is dependent on Gal/GalNAc lectin expressed on amoebae; (B) neutrophils nibble antibody-opsonized cancer cells via trogocytosis, resulting in cancer cell death (a process called trogoptosis). Trogoptosis by neutrophils is dependent on FcγR and Mac-1 integrin expressed on neutrophils.

Figure 3

The impact of trogocytosis on CD4⁺ T cell responses. Upon formation of an immunological synapse, CD4⁺ T cells acquire pMHC-II complexes from APCs. pMHC-II-dressed CD4⁺ T cells can present antigens to memory CD4⁺ T cells, resulting in T cell anergy, while their antigen presentation to naïve CD4⁺ T cells may result in differentiation into pathogenic Th17 cells. Moreover, trogocytosis by Tregs can reduce the expression of pMHC-II and co-stimulatory molecules on APCs, leading to the suppression of the CD4⁺ T cell responses elicited by interaction with APCs.

Figure 4

The impact of trogocytosis on CD8⁺ T cell responses. Upon formation of immunological synapse, CD8⁺ T cells acquire pMHC-I complexes from APCs or tumor cells. pMHC-I-dressed CD8⁺ T cells are susceptible to attack from other CD8⁺ T cells, resulting in cell lysis (fratricide). Trogocytosis reduces the expression of pMHC-I on APCs (antigen stripping). Antigen stripping in APCs favors the selective proliferation of high-affinity CTL. On the contrary, antigen stripping in tumor cells contributes to the escape from CTL attack, leading to tumor progression.

Figure 5

FcγR-mediated trogocytosis. In rituximab therapy, FcγR-expressing cells (e.g., macrophages) capture antibody-opsonized cancer cells (e.g., CLL cells), which leads to either the acquisition of CD20 by FcγR-expressing cells or a reduction in the expression of CD20 in cancer cells and escape from rituximab therapies.

Figure 6

The trogocytosis of pMHC-II in NK cells and basophils. (A) NK cells acquire pMHC-II from APCs via trogocytosis. pMHC-II-dressed NK cells rather suppress CD4⁺ T cell responses, possible because of their low expression of co-stimulatory molecules. (B) Basophils acquire pMHC-II from APCs via trogocytosis. pMHC-II-dressed basophils present antigens to naïve CD4⁺ T cells, leading to T cell proliferation and differentiation into Th2 cells with the aid of the IL-4 produced by basophils.