- Zhao ZS,
- Granucci F,
- Yeh L,
- Schaffer PA,
- Cantor H
Purpose of the Study
The onset of autoimmune disease sometimes follows an acute viral infection. One possible explanation for this phenomenon is “molecular mimicry.” According to this hypothesis, a virus could trigger autoimmunity if one of the viral proteins is very similar in structure to a host protein. Thus, an immune response to the viral protein would also initiate an autoimmune response to a similar host protein.
A mouse strain in which herpes simplex virus-type 1 (HSV-1) infection induces a chronic autoimmune keratitis.
Methods and Results
The authors cloned autoreactive T cells that target corneal antigens from mice with autoimmune herpes stromal keratitis. These T cell clones were found to also recognize part of the coat protein of herpes simplex virus-type 1 (HSV-1). Mutant HSV-1 viruses that were engineered to omit this particular protein segment (epitope) did not induce autoimmune disease.
An immune response initiated by part of the HSV-1 coat protein caused the activation of T cells that were virus-specific, but also attacked host corneal proteins that are structurally similar to the viral protein, resulting in autoimmune keratitis.
This is a convincing demonstration of molecular mimicry, and similar studies may yield groundbreaking information regarding the pathogenesis of autoimmune diseases in humans (see next review).