Amino Acid Homology Between the Encephalitogenic Site of Myelin Basic Protein and Virus: Mechanism for Autoimmunity

Abstract

Amino acid sequence homology was found between viral and host encephalitogenic protein. Immune responses were then generated in rabbits by using the viral peptide that cross-reacts with the self protein. Mononuclear cell infiltration was observed in the central nervous systems of animals immunized with the viral peptide. Myelin basic protein (MBP) is a host protein whose encephalitogenic site of ten amino acids induces experimental allergic encephalomyelitis. By computer analysis, hepatitis B virus polymerase (HBVP) was found to share six consecutive amino acids with the encephalitogenic site of rabbit MBP. Rabbits given injections of a selected eight- or ten-amino acid peptide from HBVP made antibody that reacted with the predetermined sequences of HBVP and also with native MBP. Peripheral blood mononuclear cells from the immunized rabbits proliferated when incubated with either MBP or HBVP. Central nervous system tissue taken from these rabbits had a histologic picture reminiscent of experimental allergic encephalomyelitis. Thus, viral infection may trigger the production of antibodies and mononuclear cells that cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoallergic event can take place in the absence of the infectious virus that initiated the immune response.

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

“…The microbial mimics capable of inducing EAE have been reported for all the above except for PLP. These include Herpes virus saimiri (Gautam et al, 1998), Hepatitis B virus (Fujinami and Oldstone, 1985), JC virus (Mao et al, 2007), Chlamydia pneumoniae (Conant and Swanborg, 2003), Papilloma virus (MBP mimics) (Ruiz et al, 1999), and Semliki forest virus (MOG mimic) (Mokhtarian et al, 1999).…”

Antibody Cross-Reactivity between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis

“…One mechanism discussed in this context is molecular mimicry (3); the induction of autoimmunity due to the presence of shared sequence or structural homologies with a foreign Ag (4). Many peptides derived from common viruses share linear sequence homologies with myelin proteins, and in animal models these can induce cross-reactive and potentially pathogenic T cell responses (5)(6)(7)(8)(9)(10). This cross-reactive response reflects the degeneracy of peptide-MHC complex recognition by the TCR, which allows a single receptor to bind a hierarchy of peptide ligands (6,11).…”

Evidence that Human Cytomegalovirus Assembly Protein Shares Antigenic Sites with an Uninfected Cell Membrane Protein

“…Several antibodies which cross-react with various viruses and host proteins are reviewed by Fujinami & Oldstone (1985) and Fujinami et al (1983).…”