HSP60 uses both innate and adaptive immune pathways to enhance regulatory T cell (Treg) function. (a) HSP60 and HSP60-derived epitopes are able to bind to Toll-like receptors (TLRs). By binding to TLRs present on dendritic cells (DCs), HSP60 can induce maturation of DCs or cytokine production by them [9, 11], which could possibly cause induction of Tregs. Both DCs and Tregs are able to produce IL-10, which inhibits activation of effector T cells. To suppress the ongoing immune response, HSP60-induced Tregs could inhibit activation of effector T cells (Teffs) by cell-cell contact and/or production of IL-10, or other cytokines, such as transforming growth factor β . (b) Pan-HLA-DR (pan-DR) binding HSP60 epitopes are either presented to the Tregs in a major histocompatibility complex (MHC) II molecule by DCs, which could stimulate Tregs, or they are able to bind to TLRs on the Tregs  and thereby enhance Treg function. We hypothesize that HSP60 and HSP60-derived epitopes can enhance or induce Tregs by signalling through both the T cell receptor (TCR) and TLRs at the same time. HSP60 epitopes may bind directly to TLRs on the T cells, or to TLRs on the DCs, which could indirectly enhance the immune response. (c) We hypothesize that a combination of a TCR signal by a HSP60 pan-DR binding epitope and a TLR signal by a pathogenic pattern could enhance the HSP60-induced tolerogenic response, causing a stronger and longer lasting immune regulatory effect.