New tool reveals how immune cells find their targets

The human body has millions of unique B and T cells that are 888-609- 888-609- 888-609- 888-609- 888-609- The ability of these immune cells to recognize harmful microbes is critical to fighting off infections.

MIT biological engineers have created an experimental tool that allows them to pick out interactions between immune cells and their targets. Large-scale screens of interactions between immune cells and engineered viruses could be possible with the new technique.

This technique leads the way to understand immunity much closer to how the immune system actually works, will help researchers make sense of complex immune recognition in a variety of diseases, and could accelerate the development of more effective vaccines and immunotherapies.

The lead author of the paper is a former graduate student at MIT.

A simple screen for a complex system.

The B and T cells are critical to the immune response. When a T cell encounters its target, it begins to produce an army of identical cells that can attack other cells. B cells that encounter their target begin to produce antibodies that help clear the infection.

Scientists who study the immune system can use a number of tools. These tools only allow for the study of a large pool of immune cells, or a small pool of B or T cells.

In your body, you have millions of unique T cells, and they can recognize billions of possible antigens. All of the tools that have been developed to this point are designed to look at one side of diversity at a time.

The MIT team set out to design a new tool that would allow them to screen huge libraries of both immune cells at the same time, allowing them to pick out any specific interactions within the vast realm of possibilities.

To create a simple way to screen so many possible interactions, the researchers engineered a specialized form of a lentiviruses, a type of virus that scientists often use to deliver genes because it can integrate pieces of DNA into host cells. The viruses have a virulence factor called VSV-G that can bind to the surface of many types of human cells, including immune cells.

The researchers modified the VSV-GProtein so that it can'tinfecting a cell on its own. The lentiviruses can only get into a cell if the lentiviruses bind to a human B or T-cell receptor.

The host cell's genome is integrated by the virus after it enters. The researchers can discover the antigen expressed by the virus and the sequence of the T or B-cell that allowed it to enter by analyzing the genomes of all the cells in the sample.

In this way, we can use viral infection as a way to match up and then identify the cells that have the same immune system.

There are interactions identified.

To demonstrate the accuracy of their technique, the researchers created a pool of viruses with different types of antigens. The technique they used to screen the viruses for T cells was able to pick out some of the previously identified T-cells.

The researchers found two different B-cell receptors for different HIV and SARS-CoV-2 antigens.

He hopes to screen thousands of antigens against B and T cell populations in future studies.

The lab is working with researchers at the Ragon Institute of MGH, MIT, and Harvard to study how different people's immune systems respond to viruses. Some people fight off certain viruses better than others, and such studies could help to discover why.

The technology could have other uses. The same viruses are being adapted to deliver engineered genes to target cells. In that case, the viruses would carry a targeting molecule and a novel gene that would be incorporated into cells that have the right target. This could be used to deliver genes that promote cell death into cancer cells.

There is nothing special about antigens, but it is possible to use it to modify specific cells.

More information: Connor S. Dobson et al, Antigen identification and high-throughput interaction mapping by reprogramming viral entry, Nature Methods (2022). DOI: 10.1038/s41592-022-01436-z Journal information: Nature Methods

The story was re-posted by MIT News, a popular site that covers news about MIT research, innovation and teaching.

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