The origins of autoimmune disease are multifactorial. Environmental factors and a genetic predisposition result in tissue injury caused by autoreactive T cells or antibodies. Usually a single organ or individual cell type is affected in the absence of gross abnormalities of the immune system. Autoimmune diseases tend to have long, asymptomatic prodromal periods and the initiating events leading to loss of self tolerance occur long before the disease becomes clinically manifest. This makes the initiating factors harder to identify and they remain largely unknown in humans.#### Key messages Several different pathological processes have the potential to break tolerance and cause autoimmune disease. Antigenic similarity between pathogenic organisms or foreign proteins and self proteins (molecular mimicry) is one of them. The major histocompatibility complex (MHC) is a collection of genes on chromosome 6 that codes for the human leucocyte antigens (HLA). These are glycoproteins expressed on the surface of cells that bind short peptides, degraded or generated by the cell, and present them to T lymphocytes (figs 1 and 2). The term “molecular mimicry” was used in the 1970s to explain persistent viral infections. It was suggested that the MHC and viruses encoded similar peptide sequences, which allowed the host to regard an infecting virus as “self” and forego an immune response. More recently, it has been used as a hypothesis to explain autoimmune disease.1 Several pathogens share antigenic …