Next-Gen Sequencing Enables Development of Rosetta Stone for T-Cell Language; Surprising Flexibility Revealed for T-Cell Clones

How can our immune system defend us against aggressors so diverse such as viruses, parasites, fungi, and tumors? The secret lies in the large number of clones of T and B lymphocytes, each of which expresses a particular specific receptor. Until a few years ago, deciphering the complexity of this vast repertoire was considered impossible. A "Rosetta Stone," or a key for decoding, was missing in order to “translate” and understand this "language" in all its complexity. Today, thanks to the development of new methods for DNA sequencing (Next-Generation Sequencing, NGS), it is possible to obtain millions of sequences that represent the “identity card” of T lymphocytes. But how is it possible to use this data to trace back to the specificity of the single clones, and how can we understand their function? This question has now been answered by a study published in the January 23, 2015 issue of Science and conducted by a group of researchers led by Dr. Federica Sallusto from the Institute for Research in Biomedicine of Bellinzona (Università della Svizzera italiana) in Switerland. The study describes a new approach that allows deciphering the language of T lymphocytes, which are cells of the immune system that protect us from pathogens and tumors. Combining methods of next-generation sequencing with in vitro stimulation and analysis of specific T cells, the researchers were able, for the first time, to establish a complete catalogue of the immune response to pathogens and vaccines. In particular, they have catalogued all the clones that respond to a particular microorganism, determining their specificity and their functional properties, for example their ability to produce inflammatory mediators (cytokines) or to migrate to different tissues. The research results are surprising from many points of view.
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