Data on T-cell Repertoire May Help in Understanding MS Development

T-cells in the fluid around the brain share a large percentage of receptors among different multiple sclerosis (MS) patients, a new report suggests.

Better understanding the diversity of T-cell receptors in MS, and how these cells vary in different parts of the body, could be useful in understanding the development of the disease, according to its researchers.

The study, “TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood,” was published in EBioMedicine.

A type of immune cell, T-cells play important roles in defending the body against infectious invaders. These cells also are involved in the self-targeting immune reaction that drives MS and other autoimmune diseases.

T-cells have a specialized protein receptor on their surface, aptly called the T-cell receptor or TCR. Each T-cell’s TCR will specifically recognize a particular molecular sequence, called an antigen (for example, a piece of a virus or bacteria). When a TCR binds to its specific antigen, the T-cell becomes activated, triggering an inflammatory reaction to fight the perceived threat.

Because the TCR plays a critical role in T-cell-mediated immune responses, understanding the different types of TCRs that are present in a given set of T-cells can provide important clues into these cells’ activities. The collection of TCRs among a given population of T-cells is referred to as the T-cell repertoire, as it broadly indicates the breadth of potential threats to which the T-cells can respond.

In recent years, the advent of more detailed sequencing technologies has allowed for more precise and comprehensive studies of the T-cell repertoire than ever before. Early research has indicated that the T-cell repertoire may be abnormal in people with MS. However, it hasn’t been clear whether the T-cell repertoire in the brain of MS patients differs from the repertoire elsewhere in the body.

In the new study, a team of researchers in Europe performed a series of analyses to compare the T-cell repertoire in the cerebrospinal fluid (CSF) — the fluid that surrounds the brain and spinal cord — with the repertoire in the bloodstream, called peripheral blood or PB.

Using data from prior studies, as well as new datasets, the researchers analyzed nearly 240 million different TCR sequences from 22 people with MS.

Statistical analyses did not reveal significant differences in the T-cell repertoire in the CSF or peripheral blood, which suggests, according to researchers, “that CSF does not significantly differ from PB, in terms of repertoire polarization.”

In their analysis, the researchers divided individual TCR sequences into “private” TCR sequences, which were found in only one individual, and “public” sequences, which were found in two or more individuals. The analysis revealed that individuals shared about 15% of their T-cell repertoires.

This person-to-person similarity was “unexpected,” the researchers said, “allows speculating about the role of public clones in immunity.” The team noted a need for further research into whether these shared TCR sequences may play roles in MS.

In other analyses, the researchers demonstrated that T-cells in the CSF generally had TCR sequences that were more similar to each other, compared with those in the blood. In other words, T-cells in the blood are able to recognize a more diverse array of potential threats, since they have a wider variety of TCRs, the data suggest.

“We, therefore, conclude that broad antigen recognition breadth is a repertoire quality that differs among [bodily] compartments, distinguishing CSF from PB,” the team wrote.

The researchers also compared MS T-cell repertoires with those of healthy individuals. They noted substantially more overlap in TCR sequences in the blood, compared with the CSF. The team also demonstrated that statistical analyses of the repertoires allowed them to distinguish between individuals with or without MS.

“We showed that the [TCR] clone distribution and polarization across MS repertoires may be distinguished from [healthy individuals] on the basis of the disease,” the researchers wrote.

“Our comprehensive analysis allowed us to identify those characteristics of the TCR repertoire that may be shaped by MS and by the anatomical compartment within MS cohorts [groups],” the team concluded.

Further research is needed, the scientists stressed — specifically for greater standardization in how T-cell repertoires are analyzed. Such research will make it easier to share data and make comparisons among different studies, they said.