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Institute for Research in Biomedicine
Istituto di Ricerca in Biomedicina

Via Vincenzo Vela 6 - CH-6500 Bellinzona
Tel. +41 91 820 0300 - Fax +41 91 820 0302 - info [at] irb [dot] usi [dot] ch

The language of T lymphocytes deciphered, the Rosetta Stone of the immune system

on Friday, January 23, 2015

How can our immune system defend us against aggressors so diverse among them 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?

The discovery
This question has now been answered by a study published on January 23rd in the prestigious journal Science and conducted by a group of researchers led by Federica Sallusto from the Institute for Research in Biomedicine of Bellinzona (Università della Svizzera italiana). 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 analysis of the T cell specificity and function combined with the new methods of next generation DNA sequencing represent a modern Rosetta stone to decipher the human immune response against pathogens and vaccines. The human immune response against different pathogens and vaccines comprise thousands of T cell clones of different size that can be recognized by their unique receptor sequence using the new methods of next generation DNA sequencing.

Art design: Antonino Cassotta e Mathilde Foglierini.

The research results are surprising from many points of view. First, the repertoire of specific T lymphocytes is very broad and includes thousands of clones, each characterized by a different receptor. A second unexpected result is that, within the same clone, the cells can become specialized to perform different functions and to migrate to different tissues.

According to Federica Sallusto, "using this new approach we can rapidly decipher the language of T lymphocytes, that is, their identity, specificity and function, and we can do it for the thousands of clones that mediate the immune response against microbes and vaccines. In this way we discovered that when a naive T cell recognizes a pathogen and proliferates in order to eradicate it, the progeny cells may undergo different fates, such as acquiring the ability to produce different types of cytokines or to migrate to different tissues of the organism. This extreme flexibility ofT lymphocytes represents a new element that explains how the human immune system is able to respond to attacks with different weapons and on several fronts".

This study was supported by the Swiss National Science Foundation, the European Research Council, and the European Commission.

About the Institute for Research in Biomedicine (IRB) and the Università della Svizzera italiana (USI). The Institute for Research in Biomedicine (IRB), founded in 2000 in Bellinzona, has been affiliated to the Università della Svizzera italiana (USI) in 2010. Financed by private and public institutions, and by competitive grants, the IRB currently hosts nine research groups and 100 researchers. Research focuses on the human host defense against infections, tumors and degenerative diseases. With more than 400 publications in leading scientific journals, the IRB has gained an international reputation as a center of excellence in immunology. www.irb.usi.ch

 

Article Reference

Becattini, S., D. Latorre, F. Mele, M. Foglierini, C. De Gregorio, A. Cassotta, B. Fernandez, S. Kelderman, T.N. Schumacher, D. Corti, A. Lanzavecchia, and F. Sallusto. 2014. Functional heterogeneity of human memory CD4+ T cell clones primed by pathogens or vaccines. Science. 1260668. doi:10.1126/science.1260668.