{"id":4691,"date":"2015-08-03T17:00:18","date_gmt":"2015-08-03T15:00:18","guid":{"rendered":"http:\/\/news.embl.de\/?p=4691"},"modified":"2024-04-19T15:28:00","modified_gmt":"2024-04-19T13:28:00","slug":"1508_t-cells","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1508_t-cells\/","title":{"rendered":"Know your cells"},"content":{"rendered":"\n

The T-cells that help to track down and eliminate disease-causing microbes inside our body have to be able to distinguish between invaders and our own cells. The importance of this ability becomes clear in people suffering from auto-immune diseases, in which the immune system attacks the body\u2019s own cells.<\/p>\n\n\n\n

As they mature, T-cells travel from the bone marrow to the thymus, where they are trained not to react to markers called self-antigens, which brain, muscle, and all the other cells in the body produce to identify themselves. The catch, as EMBL Heidelberg group leader Lars Steinmetz<\/a> points out, is that the \u2018trainers\u2019 are all thymic cells. \u201cIf a single thymic cell expressed everything, it would no longer be a thymic cell \u2013 it\u2019d express brain, muscle, etc., so it would lose its identity,\u201d he says. \u201cSo the system only works because each cell expresses just a few extra genes, for markers found in other tissues.\u201d<\/p>\n\n\n\n

it\u2019s not like it\u2019s thymus but also a little bit of brain<\/p><\/blockquote>\n\n\n\n

But how each cell selects those extra genes was unclear: does it not really select at all, but just randomly express some genes? Or is there some level of coordination to ensure that, by contacting different \u2018trainer\u2019 cells, a T-cell will be exposed to all the markers it needs to learn about? In a study published today in Nature Immunology<\/em>, the researchers have confirmed that it is the latter: the extra genes each cell expresses are selected in a coordinated fashion, and tend to be located close to each other in the genome.<\/p>\n\n\n\n

This study couldn\u2019t have been carried out in an individual lab<\/p><\/blockquote>\n\n\n\n

The study actually started with the Steinmetz lab\u2019s work on yeast. Bruno Kyewski from the German Cancer Research Centre (DKFZ) had seen a paper by the EMBL scientists<\/a> and reckoned that it might connect to his own findings that variation among cells was likely important in the thymus<\/a>. Around the same time, Philip Brennecke was deciding to join Steinmetz\u2019s lab at Stanford University, to work on single-cell RNA sequencing \u2013 the perfect approach to tackle the variation in gene expression in the Kyewski lab\u2019s thymic cells. And when the data started rolling in a couple of months later, bioinformatician Alejandro Reyes, a PhD student in Wolfgang Huber\u2019s lab<\/a> at EMBL, got involved.<\/p>\n\n\n\n

\u201cThis study couldn\u2019t have been carried out in an individual lab,\u201d says Steinmetz: \u201cit needs the three components: immunology, single-cell genomics and sophisticated data analysis.\u201d<\/p>\n\n\n\n

The team found that collectively, the roughly 200 cells they looked at covered around 90% of the body\u2019s self-antigens. The thymus has tens of thousands of cells, so it\u2019s very likely that when a T-cell passes through this organ, it will easily come into contact with enough variety to be exposed to virtually all self-antigens.<\/p>\n\n\n\n

\u201cBut what\u2019s also interesting is that the cells don\u2019t express the complete signatures of other tissues \u2013 it\u2019s not like it\u2019s thymus but also a little bit of brain,\u201d Steinmetz highlights. \u201cIt\u2019s more random, and that probably makes sense, because otherwise you\u2019d confuse the cell: should it be a thymus or a brain cell?\u201d Instead, the study seems to indicate that the cell randomly selects one of the areas of the genome where genes for several of these markers sit close to each other, and expresses those.<\/p>\n\n\n\n

\u201cWe believe there are several mechanisms that identify these regions of the genome, and once they have found one of those regions, that region is activated in that cell,\u201d Reyes speculates. He and his colleagues are now investigating what those mechanisms could be exactly. They suspect that the three-dimensional arrangement of genetic material, and how accessible it is to the cellular machinery that reads it, are likely to play a key role in this selection.<\/p>\n","protected":false},"excerpt":{"rendered":"

How T-cells are trained on what not to kill<\/p>\n","protected":false},"author":8,"featured_media":4694,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[28,40,42,43,49,329,44],"embl_taxonomy":[],"class_list":["post-4691","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-bioinformatics","tag-gene-regulation","tag-genomics","tag-heidelberg","tag-interdisciplinary","tag-steinmetz","tag-transcription"],"acf":{"article_intro":"

They are soldiers on patrol, on the lookout for invaders. But first of all, they must learn who not to kill.<\/p>\n","related_links":[{"link_description":"Steinmetz's lab at Stanford","link_url":"https:\/\/web.stanford.edu\/group\/steinmetzlab\/cgi-bin\/wordpress\/"},{"link_description":"Kyewski lab - DKFZ","link_url":"https:\/\/www.dkfz.de\/en\/entwicklungsimmunologie\/index.php"},{"link_description":"Approved treatment boosts natural defense to auto-immune disorders","link_url":"http:\/\/news.embl.de\/science\/1410_autoimmune_disorders\/"}],"article_sources":[{"source_description":"

Brennecke, P., Reyes, A., Pinto, S. et al<\/em>. Nature Immunology<\/em>, 3 August 2015. DOI: 10.1038\/ni.3246<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1038\/ni.3246"}],"vf_locked":false,"featured":false,"color":"#007B53"},"embl_taxonomy_terms":[],"yoast_head":"\nKnow your cells | EMBL<\/title>\n<meta name=\"description\" content=\"In the thymus, T-cells are trained not to react to markers produced by brain, muscle and other cells. 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