HFE, although does not bind peptides, is recognized by the T-cell receptor of a specific subset of CD8+ T-cells in mice and is able of shaping the T-cell repertoire.[9–11] Moreover, HFE, through its α1/α2 domains, seems to be a negative regulator of CD8+ T-cell activation, reducing the release of several soluble factors like macrophage inflammatory protein-1β and interferon (IFN)-Υ and reducing the expression of markers of T-cell activation: this could have clear implications in the immune response to pathogens and autoimmune diseases.[12]. Here, HFE is linked to autoimmune disease.