Image courtesy of NIAID
A new tool can help scientists determine how different types of T cells detect, destroy, and remember antigens, according to research published in Nature Methods.
The tool is TraCeR, a computational method that allows researchers to reconstruct full-length, paired T-cell receptor sequences from single-cell RNA sequence data.
TraCeR reveals clonal relationships between T cells as well as their transcriptional profiles.
In the current study, TraCeR helped scientists detect T-cell clonotypes in mice infected with Salmonella.
“This new tool for single-cell sequencing gives us a new approach to the study of T cells and opens up new opportunities to explore immune responses in disease, vaccination, cancer, and autoimmunity,” said study author Sarah Teichmann, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.
She and her colleagues noted that T-cell receptors are extremely variable, and a combination of paired sequences determines which protein a receptor will detect. So to understand what is happening at the molecular level, it is imperative to find both sequences in each cell.
TraCeR is designed to allow scientists to look at the DNA and RNA profiles of these highly variable T-cell receptors at the same time.
Dr Teichmann and her colleagues found that receptor sequences are unique, unless the T cells have the same parent cell. The presence of “sibling” cells proves that an infection has triggered the division of a particular T cell, which indicates it is multiplying to fight an antigen.
Using TraCeR, the researchers were able to accurately identify sibling T cells and explore their different responses to Salmonella infection in mice.
“This technique helps us see whether all the ‘children’ of a particular T cell do the same thing at the same time, which is an open question in biology,” said study author Tapio Lönnberg, PhD, of the European Molecular Biology Laboratory-European Bioinformatics Institute in Cambridge, UK.
“We can start to see whether the antigen itself plays a role in how a T cell will respond, and even whether it’s possible to determine what the invader is, just based on the sequence of a T-cell receptor.”
The researchers said their next step is to apply similar methods to the study of B cells to better understand the adaptive immune system as a whole.
