New role for Agrin in T cells and its potential importance in immune system regulation

Abstract

Agrin plays a crucial role in the maintenance of the neuromuscular junction. However, it is expressed in other tissues as well, including T lymphocytes, where cell activation induces its expression. Agrin from activated T cells has the capacity to induce aggregation of key receptors and to regulate signalling. Interestingly, T cells isolated from patients with systemic lupus erythematosus over-express Agrin and its co-stimulation with the T cell receptor enhances production of pathogenic cytokines. These early studies point to an important function for Agrin in T cell biology and make the case for a more thorough and systematic investigation into its role in the immune system.

Figure 1

Depiction of the secreted and transmembrane forms of the Agrin protein. Various structural domains of the protein are indicated by differential colouring.

Figure 2

Agrin localization in T cells during their in vitro activation. Confocal picture of a conjugate between a human CD4⁺ T cell and an anti-CD3/CD28-coated stimulatory bead. Agrin was visualized with the m247 anti-Agrin antibody.

Figure 3

Schematic illustration showing a potential function for Agrin in the context of the immunological synapse. The organization of key surface receptors is illustrated in the context of the mature immunological synapse structure during antigen presentation or in the absence of stimulation. Agrin is shown in its fully glycosylated (no activation) and modified (activation) forms. Also shown is a hypothetical receptor for Agrin expressed by the antigen presenting cell (APC). ICAM, intracellular adhesion molecule; LFA, lymphocyte function-associated antigen; MHC, major histocompatibility complex.