Conventional and non-conventional antigen presentation by mast cells

Abstract

Mast cells (MCs) are multifunctional immune cells that express a diverse repertoire of surface receptors and pre-stored bioactive mediators. They are traditionally recognized for their involvement in allergic and inflammatory responses, yet there is a growing body of literature highlighting their contributions to mounting adaptive immune responses. In particular, there is growing evidence that MCs can serve as antigen-presenting cells, owing to their often close proximity to T cells in both lymphoid organs and peripheral tissues. Recent studies have provided compelling support for this concept, by demonstrating the presence of antigen processing and presentation machinery in MCs and their ability to engage in classical and non-classical pathways of antigen presentation. However, there remain discrepancies and unresolved questions regarding the extent of the MC's capabilities with respect to antigen presentation. In this review, we discuss our current understanding of the antigen presentation by MCs and its influence on adaptive immunity.

Keywords: CD4 T cell; CD8 T cell; DC; antigen presentation; mast cells.

Graphical Abstract

Figure 1:

MHC-II expression on MCs. MCs have low surface expression of MHC-II in the steady state, where most of the MHC-Il molecules are stored in the intra-granular vesicles. After activation of MCs, MHC-II surface expression increases when intracellular vesicles fuse with the plasma membrane. Diagram was created with Biorender.com.

Figure 2:

MC-dependent T cell activation and differentiation. (A) MCs can take up and process exogenous antigens. Stimulation of MCs by degranulating stimuli boosts MHC-Il-mediated Ag presentation, where processed antigens can then be loaded on to MHC-lI molecules, presented to CD4 T cells and activate them. Co-stimulatory interactions similar to those used by APCs and some that are yet to be defined also likely contribute to naïve T cell activation. (B) Tissue-resident MCs have been shown to secrete vasoactive mediators and chemokines to promote extravasation and recruitment of immune cells, including T cells to the site of inflammation. MCs also promote LN swelling or hypertrophy, which can promote efficient adaptive immune responses. (C) CD4 T cell polarization can be MC-dependent, and the skewing of different CD4 subsets varies between studies. Diagrams were created with Biorender.com.