Next-Gen Sequencing Used to Identify Nearly All T-Cell Receptor Variants in Blood Samples

Researchers say that they have identified essentially all T-cell receptor variants in blood samples. Using next-generation sequencing technology, they revealed more than 1 million unique sequences.

Details are published in Genome Research, and the paper is titled “Exhaustive T-cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes.”

The researchers found that some T-cell receptor sequences are common, some are rare, and the repertoire can change over time. The individual repertoire was then compared to that of two other individuals, showing that only a minority of sequences is shared between them.

For sequences that are shared different gene-shuffling events often generated the same sequence, the study also found. "This shows that certain sequences are more favored than others, most likely because they are more effective in recognizing specific types of infections or mutations," says the paper's senior author, Robert Holt, Ph.D., of the BC Cancer Agency and Simon Fraser University.

Until now, no study had captured the entire range of sequences in immune cell repertoires present in an individual sample, though their diversity has been previously investigated. Dr. Holt points out that his researched showed that while there is high T-cell diversity in a standard blood sample, it does not give the entire picture.

“This is only part of the diversity that would be present within a person's entire body,” Dr. Holt says. “But now we know that although the diversity is very large, it is ultimately limited, and it is measureable.”

Future studies, Dr. Holt says, will recognize how the repertoire is disturbed in cases of immune challenge such as infectious disease or organ transplantation through comparison with the baseline diversity of the immune repertoire in a healthy individual.