{"id":11602,"date":"2016-11-21T00:00:26","date_gmt":"2016-11-21T08:00:26","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=11602"},"modified":"2024-01-30T15:23:39","modified_gmt":"2024-01-30T23:23:39","slug":"immune-receptors-amplify-invader-signals-turning-mini-machines","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/immune-receptors-amplify-invader-signals-turning-mini-machines\/","title":{"rendered":"Immune receptors amplify \u201cinvader\u201d signals by turning into mini-machines"},"content":{"rendered":"
\"immune-receptors-amplify-invader-signals-by-turning-into-mini-machines\"
Salk Institute scientists discover how Immune receptors use a protein called ZAP70 to amplify \u201cinvader\u201d signals and attack a biological intruder. Single molecule tracks of Zap70 overlaid with T cell receptor microclusters shows signal transfer at early moments of T cell activation.<\/p>\n

Click here<\/a> for a high-resolution image.<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

LA JOLLA\u2014When a receptor on the surface of a T cell\u2014a sentry of the human immune system\u2014senses a single particle from a harmful intruder, it immediately kicks the cell into action, launching a larger immune response. But exactly how the signal from a single receptor, among thousands on each T cell, can be amplified to affect a whole cell has puzzled immunologists for decades.<\/p>\n

Now, Salk scientists have discovered the key to the amplification of an \u201cinvader\u201d signal. The T cell receptor that detects the intruder turns into a mini-machine, activating and releasing copy after copy of a protein called ZAP70. The finding, published in Nature Immunology<\/em><\/a> on November 21, 2016, could help scientists design better immune-mediated treatments for \u764c\u75c7<\/a> or autoimmune diseases<\/a>.<\/p>\n

\u201cThis is really the first amplification method that\u2019s been found at this level of the immune response,\u201d says senior author Bj\u00f6rn Lillemeier<\/a>, an associate professor in Salk\u2019s Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis and the Waitt Advanced Biophotonics Center. \u201cIt answers a longstanding question that has bugged immunologists for more than three decades.\u201d<\/p>\n

T cells are central in the adaptive immune response, which is the body\u2019s ability to recognize pathogens and respond to them. A single T cell\u2019s receptors screen thousands of molecules at any given second, but most of them originate from the body\u2019s own proteins and have to be ignored as \u201cself.\u201d Researchers have struggled to explain how, in the wake of overwhelming \u201cself\u201d signals, a T cell can detect and respond to one or two \u201cinvader\u201d signals.<\/p>\n

Lillemeier\u2019s lab studied ZAP70, a protein that associates with T cell receptors and becomes activated when the receptors recognize a foreign molecule. To track the activity and location of ZAP70 molecules, the team tagged them with a fluorescent marker while anchoring each T cell receptor in place. To the group\u2019s surprise, ZAP70 molecules were being activated by the T cell receptors and then moving away, spreading throughout the cell.<\/p>\n

\u201cThis is a completely different method of amplification than we expected,\u201d says Zachary Katz, a research associate in the Lillemeier lab and first author of the new work. \u201cEveryone always thought the amplification would be determined by the interaction between the foreign molecule and the T cell receptor, but this is happening downstream of the receptor.\u201d<\/p>\n

\"lucie-novotna_amy-blount_bjorn-lillemeier_zachary-katz_0x8c5462\"<\/a>
From left: Lucie Novotna, Amy Blount, Bj\u00f6rn Lillemeier and Zachary Katz<\/p>\n

Click here<\/a> for a high resolution image<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

By churning out ZAP70 and sending it throughout the cell\u2014as opposed to just activating a handful of ZAP70s and keeping them tethered to the T cell receptor\u2014the immune cells can rapidly spread a signal throughout the cell.<\/p>\n

\u201cWhat we saw is that at the beginning of signaling, you have lots of ZAP70 being released from the T cell receptor to amplify and distribute the signal,\u201d says Lillemeier. \u201cBut once the signaling is established, the T cell receptor actually adapts and stops releasing so much of ZAP70.\u201d<\/p>\n

Questions remain on how the process works, including what the ultimate destinations of the ZAP70 molecules are and how they go on to transmit signals. But the observation, Lillemeier says, is progress toward understanding how T cells identify and react to pathogens.<\/p>\n

\u201cIt\u2019s really important to understand this process since T cells are at the center of the adaptive immune response,\u201d he says. \u201cIf the receptors are not controlled well, you\u2019re sick; you might either have an autoimmune disease or you can\u2019t respond to infections.\u201d Being able to make the receptors have a stronger or weaker signal\u2014perhaps by changing how much ZAP70 they activate and release\u2014could help treat these kinds of diseases, he adds.<\/p>\n

Other researchers on the study were Lucie Novotn\u00e1 and Amy Blount of the Salk Institute.<\/p>\n

The work and the researchers involved were supported by grants from the Nomis Foundation<\/a>, the Waitt Foundation<\/a> and the James B. Pendleton Charitable Trust, the National Institutes of Health<\/a>, a Pioneer Fund Postdoctoral Scholar Award, the Salk Institute Cancer Center<\/a> core facilities funded by the National Cancer Institute<\/a> and the Mass Spectrometry Core of the Salk Institute supported by the Helmsley Center for Genomic Medicine<\/a>.<\/p>","protected":false},"featured_media":11605,"template":"","faculty":[97],"disease-research":[46],"class_list":["post-11602","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-bjorn-lillemeier","disease-research-cancer-biology"],"acf":[],"yoast_head":"\nImmune receptors amplify \u201cinvader\u201d signals by turning into mini-machines - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/immune-receptors-amplify-invader-signals-turning-mini-machines\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Immune receptors amplify \u201cinvader\u201d signals by turning into mini-machines - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"Salk Institute scientists discover how Immune receptors use a protein called ZAP70 to amplify \u201cinvader\u201d signals and attack a biological intruder. 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