Spike protein has some common motifs with human proteins, including a five-amino acid stretch (TQLPP)
with antigenic properties that are homologous with a sequence found in thrombopoietin, and the ELDKY
motif that is shared with tropomyosin and with Protein Kinase cGMP-dependent type 1 (PRKG1), a kinase
involved in platelet activation and calcium regulation.
Molecular mimicry is one of the mechanisms hypothesized to explain the development of autoimmune
disease. An important concern is whether mRNA vaccination for Spike protein production could result in
a breakdown in tolerance and the development of autoimmune disease due to molecular mimicry. The
risk increases with frequent and close administrations of the vaccine, which challenge the immunogenic
versus tolerogenic state of the immune system.
In this condition, proinflammatory cytokines can alter the control of immunoregulatory circuits so that
autoreactive T cells can become effective and trigger autoimmunity. In addition, the "homologies"
between the Spike protein and human proteins are much greater than for other viruses and bacteria,
increasing the risk of developing autoimmune diseases.
The issue of interactions between the immune system and ACE2 (or other virus receptors) is further
complicated when considering that the immune system is complex and dynamic.
For example, the formation of anti-idiotype antibodies and lymphocytes is one possible explanation for
the persistence of typical COVID-19 symptoms even after the virus has been eliminated from the body.
Indeed, anti-idiotype antibodies (Ab2 in the Figure below), which reflect the Spike epitope, can bind to
ACE2 or similar structures and cause the pathophysiological reaction of long Covid.
This phenomenon can occur with SARS-CoV-2 infection as well as with anti-COVID-19 vaccines, explaining
at least in part the persistence of adverse reactions in some individuals. It has also been suggested that
anti-idiotype antibodies might bind to neuropilin-1, which is recognized by the SARS-CoV-2 virus Spike,
and this might explain some neurological adverse effects such as the peripheral neuropathy that arises
after vaccination with BNT162b2.