The major histocompatibility complex(MHC) is the exclusive chaperone that presents intracellular antigens,either self or foreign to T cells.Interestingly,aberrant expression of MHC molecules has been reported in various autoimmune target tissues such as thyroid follicular cells in Grave’s disease.Herein,we review the discovery of an unexpected effect of cytosolic doublestranded DNA(ds DNA),despite its origins,to induce antigen processing and presenting genes,including MHC molecules,in non-immune cells.Moreover,we highlight several recent studies that suggest cell injury endows thyroid epithelial cells with a phenotype of mature antigen presenting cells by inducing multiple antigen processing and presenting genes via releasing genomic DNA fragments into the cytosol.We discuss the possibility that such cytosolic ds DNA,in naked form without binding to histone proteins,might be involved in the development of cell damage-triggered autoimmune responses.We also discuss the possible molecular mechanism by which cytosolic ds DNA can induce MHC molecules.It is reasonable to speculate that cytosolic ds DNA-induced MHC class Ⅰ is partially due to an autocrine/paracrine effect of type Ⅰ interferon(IFN).While the mechanism of cytosolic ds DNA-induced MHC class Ⅱ expression appears,at least partially,distinct from that mediated by IFN-γ.Further in-depth are required to clarify this picture. The major histocompatibility complex (MHC) is the exclusive chaperone that presents intracellular antigens, either self or foreign to T cells. Specifically, aberrant expression of MHC molecules has been reported in various autoimmune target tissues such as thyroid follicular cells in Grave’s disease. Herein, we review the discovery of an unexpected effect of cytosolic double stranded DNA (ds DNA), despite its origins, to induce antigen processing and presenting genes, including MHC molecules, in non-immune cells. More over, we highlight several recent studies that suggest cell injury endows thyroid epithelial cells with a phenotype of mature antigen presenting cells by inducing multiple antigen processing and presenting genes via releasing genomic DNA fragments into the cytosol. We discuss the possibility that such cytosolic ds DNA, in naked form without binding to histone proteins, might be involved in the development of cell damage-triggered autoimmune responses.We also discuss the possible molecular mechanism by which cytosolic ds DNA can induce MHC molecules. It is reasonable to speculate that cytosolic ds DNA-induced MHC class I is partially due to an autocrine / paracrine effect of type I interferon (IFN). Whilst the mechanism of cytosolic ds DNA- induced MHC class II expression appears, at least partially, distinct from that mediated by IFN-γ. Further in-depth are required to clarify this picture.