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

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