Unlike GVHD induced by mature T cells transferred in human PBMCs (Brehm et al., 2019), the slowly evolving autoimmune disease (termed autoimmune because it is mediated by T cells developing de novo in the recipient rather than by cells carried in the graft) in Hu/Hu mice is independent of direct recognition of murine antigens, as it develops with similar velocity in NSG mice that express MHC and in those that completely lack (due to β2m and CIITA knockout) murine Class I and Class II MHC antigens (Khosravi-Maharlooei et al., 2021). Here, B2M is linked to autoimmune disease.