In a recent study led by Dr. Hisashi Arase published in Cell, a new mechanism underlying the breakdown of self-tolerance in systemic lupus erythematosus was reported that autoreactive T cells recognize neoself-antigens. Neoself-antigens, encompassing a range of self-molecules, were shown to be presented on major histocompatibility complex class II by non-canonical mechanisms following the downregulation of the invariant chain protein.