T regulatory cells mediate specific suppression by depleting peptide-MHC class II from dendritic cells

T regulatory cells (T(regs)) can activate multiple suppressive mechanisms in vitro upon activation via the T cell receptor resulting in antigen-independent suppression. However, it remains unclear whether similar pathways operate in vivo. Here, we found that antigen-specific T(regs) activated by dendritic cells (DCs) pulsed with two antigens suppressed T(naive) specific for both cognate and non-cognate antigens in vitro, but only suppressed T(naive) specific for cognate antigen in vivo. Antigen-specific T(regs) formed strong interactions with DC resulting in selective inhibition of the binding of T(naive) to cognate antigen, yet allowing bystander T(naive) access. Strong binding resulted in removal of the cognate peptide-MHCII (pMHCII) from the DC surface reducing the capacity of the DC to present antigen. The enhanced binding of T(regs) to DC coupled with their capacity to deplete pMHCII represents a novel pathway for T(reg)-mediated suppression and may be a mechanism by which T(regs) maintain immune homeostasis.