The influence of antigen recognition on Treg suppressive function

Abstract

Abstract Tregs play an essential role in preventing autoimmunity by maintaining effector T cell balance and self-tolerance. Antigen stimulation through T cell receptor (TCR) makes Treg suppression more efficacious and as such is generally viewed as a strong predictor of Treg function. In demyelinating disease Tregs with the most effective suppressive capacity are self-antigen specific, however, it is unclear how the parameters of self-antigen stimulation (affinity, force, and bond lifetime) modulate Treg suppressive potency. Here we utilize the well-described myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide driven experimental autoimmune encephalomyelitis (EAE) to address how Treg self-antigen interactions under chronic inflammation influence suppressive potency. Recently Tregs have been shown to perform trogocytosis to remove MHC molecules from the surface of antigen presenting cells in an antigen specific manner. We hypothesize that trogocytosis correlates with optimal Treg antigen specific suppression in demyelinating disease. To test suppressive capacity of self-antigen specific Tregs we utilized a MOG knockout mouse model of EAE. In this system we show that MOG knockout Tregs are less potent suppressors when challenged with EAE despite identical affinity for MOG35–55 as wild type Tregs. In addition, we show that MOG knockout Tregs perform trogocytosis less readily than wild type Tregs demonstrating that the presence of self-antigen MOG35–55 is necessary for development of optimal Treg generation. An understanding of how Tregs respond to antigen may allow the design of therapeutic strategies to better harness Treg power in combatting autoimmune conditions. Supported by grants from NIH (5R01NS071518-09)