"Public" T-Cell Receptors From Resistant People Fend Off HIV

During the study of blood samples of "elite controllers" by a group of microbiologists from Australia, special cellular receptors were discovered that allow the body of these people to keep HIV under control. According to experts, the immune system of every person can be "tuned" in such a way as to successfully resist the virus.

Researchers led by Dr. Stephanie Gras of the University of Monash, Australia, told Scientist that they were able to identify an unusual receptor in T cells that can recognize low HIV levels and give the virus an adequate response. Gras believes that the results of the work published on June 8 in Science Immunology can be a new milestone in the development of immunotherapy against HIV.

Andrea De Maria, an infectious disease specialist from the University of Genoa in Italy, noting the importance of the discovery, indicated that his findings "may open the possibility of immunotherapy similar to adaptive cell therapy (CAR T-Cell Therapy), an extremely promising method of fighting against tumors and malignant neoplasms.

As you know, in the world there are less than 1% of people living with HIV who are "elite controllers" - people who do not need ARVT to keep the virus under control.

Australian specialists who previously conducted a study of this group of patients managed to establish that the T-cells of the controllers were more likely to have a so-called "open" receptor.

Unlike most T-cell receptors (TCRs), which are "closed" and activated only when they come into contact with the corresponding human leukocyte antigen (HLA), carrying a portion of the virus or other potential threat, "open" receptors are able to recognize the HLA array. Moreover, according to Grasse, the same receptor was detected immediately by several people.

"We all have about 100 million different TCRs, and it's almost impossible to find the same receptor in two people. We found the same TCR from six different people, and they were all controllers, "she said.

In the course of their research, scientists examined the effect of "open" TCRs on the immune response (HIV) and tried to establish that it allows them to activate several HLAs at once.

As experts noted, in the culture of CD4 + and CD8 + T cells, armed with only one of the "open" TCR, the immune system effectively recognized and destroyed HIV-infected dendritic cells.

The researchers also determined the structure of complexes formed under conditions of interaction of "open" TCR with different HLA containing HIV particles. The researchers found that each TCR contact was mainly with a peptide derived from HIV, not HLA itself.

According to Dr. Grasse, the discovery is really important for the future treatment of HIV infection, since using "open" TCR for T cells will be possible for completely different people with their own genetics.

The team of microbiologists is planning in the near future to begin testing the complex on humanized rodent models.

Some experts, however, look at the opening with restrained optimism. Thus, Andrea De Maria warns that "open" TCRs alone do not explain the phenomenon of the "elite controller" and can not mimic their protection, because "there is no single mechanism that probably helps control HIV."

"This article allows you to learn more about the role of CD4 + T cells in facilitating control, and this can be a new aspect that will be taken into account when developing therapeutic HIV vaccines," says Peter Hunt, an HIV researcher at the University of California San Francisco, USA).

An alternative way to use the discovery, says Joel Blankson of the Johns Hopkins University School of Medicine, will be the inclusion of a peptide derived from HIV that caused a strong T cell response - the highly conserved region of the Gag293 capsid protein - into the vaccine.

"I think immunization with an epitope would be effective," Scientist said, "but if people did not respond to it, then perhaps the second option would be to transduce" open "T cell receptors in those patients, the immune system who did not react. "