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Scientists discover that natural killer cells can regulate anti-HIV antibody production
In developing vaccines to stimulate immune responses to prevent HIV infection, researchers have been focused on finding or producing a specific antibody that neutralizes the virus. These broadly neutralizing antibodies (bnAbs) are eventually produced in approximately 50% of HIV-infected patients, but they are produced too late to be effective against HIV because they have been repeatedly mutated and inserted into the HIV virus. The patient's genome is gone.
If a method is found that produces bnAbs before HIV infection, then they can suppress the HIV infection, and researchers from the Duke Human Vaccine Institute have recently succeeded in finding an important protein. The human body that produced bnAbs is highly active. This protein, called RAB11FIP5, is involved in the distribution and function of natural killer cells, which are the first immune cells to respond during viral infection. Natural killer cells also play an important role in autoimmune diseases.
"I didn't know that this immune cell can regulate bnAbs," said the study's senior author, Professor Barton Haynes of the Duke Human Vaccine Institute. "We have discovered a new pathway for natural killer cells to carry cargo, which seems to play an important regulatory role in regulating the production of bnAbs."
Haynes and his colleagues designed experimental analysis of the molecular differences between HIV-infected and non-infected individuals who can produce bnAbs. They analyzed 239 infected people and found that they were almost two extremes - half of them had extremely high bnAbs and the other half were extremely low. The researchers used RNA sequencing to determine the molecular differences associated with antibody production and found significant differences in RAB11FIP5 gene expression.
"These data suggest that natural killer cells regulate the production of bnAbs, and Rab11 is a regulator of HIV antibody response," said author Todd Bradley. "This is a new signaling pathway, and we hope that this pathway can be modulated during the vaccination process to produce a better HIV antibody response."
Reference: Todd Bradley et al. RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses.Cell.DOI: https://doi.org/10.1016/j.cell.2018.08.064