February 24, 2011 – T-cell receptor diversity in blood samples from healthy individuals has been extensively cataloged for the first time in a study published online today in Genome Research (www.genome.org), setting the stage for a better understanding of infectious disease, cancer, and immune system disorders.
Adaptive immunity is mediated by T-cells, a white blood cell that identifies and attacks cells that may be infected with viruses or contain cancer-causing mutations. To recognize a wide array of potentially infectious agents or cancer-causing mutations, gene shuffling creates a highly variable and diverse collection of T-cell receptor sequences.
While the diversity of sequences in immune cell repertoires has been investigated previously, no study had yet been able to capture the entire range present in an individual sample. Now, using next-generation sequencing technology, researchers in Canada have identified essentially all T-cell receptor variants in blood samples, identifying more than one million unique sequences.
Dr. Robert Holt of the BC Cancer Agency and Simon Fraser University, senior author of the report, explained that this study is the first to establish 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," Holt said, "but now we know that although the diversity is very large, it is ultimately limited, and it is measureable."
The group 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.
Interestingly, they noted that for sequences that were shared, different gene shuffling events had often generated the same sequence. "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," said Holt.
By cataloging the baseline diversity of the immune repertoire in a healthy individual, Holt explained that future studies would be able to then recognize how the repertoire is disturbed in cases of immune challenge, such as infectious disease or organ transplantation, and furthermore, may assist in the development of new vaccines.
Scientists from the British Columbia Cancer Agency (Vancouver, British Columbia, Canada) and Simon Fraser University (Burnaby, British Columbia, Canada) contributed to this study.
This work was supported by the Canadian Institutes of Health Research, Genome Canada, and Genome British Columbia.
The authors are available for more information by contacting Cher Sawchuk, Communications Leader at the BC Cancer Agency (firstname.lastname@example.org; +1-778-778-6643) or Carol Thorbes, Information Officer at Simon Fraser University (email@example.com; +1-778-782-3210).
Interested reporters may obtain copies of the manuscript from Peggy Calicchia, Editorial Secretary, Genome Research (firstname.lastname@example.org; +1-516-422-4012).
About the article:
The manuscript will be published online ahead of print on February 24, 2011. Its full citation is as follows: Warren RL, Freeman JD, Zeng T, Choe G, Munro S, Moore R, Webb JR, Holt RA. 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. Genome Res doi: 10.1101/gr.115428.110.
About Genome Research:
Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.
About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory is a private, nonprofit institution in New York that conducts research in cancer and other life sciences and has a variety of educational programs. Its Press, originating in 1933, is the largest of the Laboratory's five education divisions and is a publisher of books, journals, and electronic media for scientists, students, and the general public.
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