Study identifies an enzyme crucial for the immune response: A breakthrough in medical research

A group of immunologists from t the IRCM, Montréal recently delineated the mechanism affecting AID, activation-induced deaminase, a vital enzyme responsible for immune response.

The study was based on B-lymphocytes, mainly producing antibodies to fight against infections. The team focussed on AID, crucial for an efficient antibody response.

They previously detected a very abundant cellular protein, Hsp90, which helped in stabilizing immature AID and maintaining its levels. Moreover, high levels of AID had been shown to have deleterious consequences, as it could lead to certain cancer-causing mutations. Thus to maximise the protective effects of AID while reducing the damaging risk the team focussed to find out the perfect level of AID.

The team also identified another protein, eEF1a, which helped AID to retain in cell’s cytoplasm and maintained AID’s active state, away from the genome. Therefore by blocking of AID-eEF1a interaction would help AID to access the cell-nucleus. Thus activity of AID would be enhanced and immune response would be amplified. Actually eEF1a functioned as a buffer.  It allowed the cell to accumulate enough AID to be efficient, but limited AID’s activity to prevent the oncogenic effects too by preventing continuous contact of AID with the genome.

The IRCM scientists also identified two existing drugs that can act on eEF1 to release AID into the cell. They could potentially be used to boost AID activity and, thus, the immune response.

Thus the experts think that this discovery, the activity of AID with in cells could be regulated by targeting different proteins. This knowledge would eventually lead to develop new treatment strategies to boost our immune system and  thereby enhancing our ability to fight against en-numerous diseases and pathogens.  AID activity decreases with age, therefore this knowledge would help the aging population to stay healthy. On the other hand, toxic effects associated with high levels of AID can also be lowered in certain cancers such as B-cell lymphoma and leukaemia, by therapies based on this mechanism.

Reference:

Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm. S.P. Methot, L.C. Litzler, F. Trajtenberg, A. Zahn, F. Robert, J. Pelletier, A. Buschiazzo, B.G. Magor, and J.M. Di Noia. doi: 10.1084/jem.20141157.

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Arunima Maiti

Arunima Maiti

Biomedical scientist with special interest in reproductive biology.

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