Human T-cell repertoire analysis
T-cell receptors, like antibodies, are encoded by genes that undergo random somatic recombination to generate sequence diversity and consequently structural diversity. The structural diversity of the T-cell receptor allows T-cells to recognize an enormous number of foreign antigens. In this study, scientists at the Genome Sciences Centre have profiled to an unprecedented depth the repertoire of rearranged T-cell receptor beta chain sequences in the peripheral blood of three healthy individuals. They obtained over one million distinct T-cell receptor nucleotide sequences from a single individual which establishes a new, directly measured lower limit on individual T-cell repertoire size and provides a useful reference set of sequences for repertoire analysis. A key observation is that there is much higher sharing of specific T-cell receptor sequences among individuals than expected by chance, and these shared sequences show a strong signature of selection, where a given amino acid sequence may be encoded by multiple different nucleotide sequences. The study also presents an analysis of the impact of sequencing error on repertoire analysis, and reports an error handling strategy that will be important for understanding future deep sequencing studies of immune repertories. Ongoing work involves characterization of immune repertoire changes in response to immune challenges from, for example, cancer, autoimmune disease, and bone marrow transplant and vaccination.
René L. Warren1, J. Douglas Freeman1, Thomas Zeng1, Gina Choe1, Sarah Munro1, Richard Moore1, John R. Webb2, Robert A. Holt1,3. 2011. 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 Research. doi:10.1101/gr.115428.110
1BC Cancer Agency, Michael Smith Genome Sciences Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3 Canada
2BC Cancer Agency, Deeley Research Centre, 2410 Lee Ave, Victoria, BC V8R 6V5 Canada
3Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada
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