Molecular mimicry involves two or more unrelated molecules that mimic each other – for example, a viral protein may mimic a human protein. Why? A small portion of the viral protein may be very similar or identical to a small portion of the human protein. It is said that, in molecular mimicry, a protein “impersonates” another one.
If an antibody or a T-cell receptor is directed against that small portion of the viral protein, it will also bind the similar portion of the human protein. Sometimes this is called “mistaken identity”.
We can say that, in molecular mimicry, one protein impersonates another one, leading to a case of mistaken identity.
In our case, the viral protein is the hemagglutinin of the H1N1 swine influenza virus, and the human protein is hypocretin (also called orexin). Hemagglutinin is present on the surface of the influenza virus and is responsible for binding the cell that is being infected. Hypocretin is a neuropeptide produced by some of the neurons located in a brain region called the hypothalamus. It keeps us awake by sending appropriate signals to other regions of the brain.
In 20o9, the H1N1 swine influenza pandemic swept our planet. In 2010, an unexpected increase in narcolepsy incidence was observed in China — in areas in which the H1N1 influenza virus had spread the previous year. An increase in narcolepsy incidence was also reported in Europe — in children vaccinated with Pandemrix, a vaccine developed to control the swine flu.
The increase in the incidence of narcolepsy related to infections in China and to vaccination in Europe came on quickly, and since 2010, has steadily decreased — likely because the H1N1 swine flu pandemic ended and Pandemrix has not been used since.
A study recently published in Science Translational Medicine (December 18, 2013) shows that patients with narcolepsy — when given a seasonal influenza vaccine containing the H1N1 hemagglutinin — react by activating CD4+ T cells. The researchers isolated the activated CD4+ T cells from the patients’ blood, exposed the cells to hypocretin, and discovered that they reacted to this molecule.
These results provide evidence of molecular mimicry between H1N1 hemagglutinin and hypocretin and suggest that, in patients able to recognize the shared portion of these two molecules, an auto-immune response might lead to the loss of neurons that produce hypocretin. Although the specific mechanisms responsible for neuron loss are not clear, the researchers suggest that this process leads to narcolepsy, which develops when the neurons that produce hypocretin are destroyed.
The proposed working model is that narcolepsy occurs in people with a genetic predisposition, following exposure to an environmental factor that triggers an immune response directed to hypocretin. The 2009 H1N1 influenza virus was such a factor, and the genetic predisposition is due to the person carrying a specific form of one of the human leukocyte antigen (HLA) genes.
The researchers suspect that other viruses or pathogens could occasionally cause similar cases of mistaken identity. Indeed, molecular mimicry may not be as uncommon as once thought.
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