Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Linking the immune system with lipid metabolism

19.12.2003


A team of researchers led by scientists at The Scripps Research Institute has discovered a family of proteins that connect the immune system to the body’s lipids - the fat molecules that are a major building block of the human body.



"This is the first time someone has shown how the immune system and lipid metabolism merge," says Associate Professor Luc Teyton, M.D., Ph.D., of Scripps Research. Teyton is the lead author of the study.

In the study, Teyton and his colleagues were examining what is known as a natural killer (NK) T cell. NK T cells are key players in the immune system and have been implicated in autoimmune diseases, such as diabetes, and in cancer--although scientists have not yet discerned exactly how.


NK T cells are unusual in that they fall somewhere between innate and adaptive immunity. They arise in the thymus, and, as mature cells, they stimulate an adaptive immune response and regulate a range of disease states, including diabetes, cancer, and pathogenic infections.

Like other T cells, they express T cell receptors (TCR)--although without the normal antigenic variability. Classical immune recognition involves a process in which variable TCRs recognize various proteins--pieces of protein from foreign pathogens, for instance--when these are presented by "antigen presenting cells" via a molecule called the major histocompatability complex (MHC). MHC molecules are like the burglar alarms that warn the immune system that a pathogen is invading.

However, NK T cells also express the "NK" innate immune cell receptors and may have the ability to see some of the lipids that bacteria like Mycobacterium tuberculosis, the bacteria that cause tuberculosis, display on their outer surface. NK T cells become activated when they bind to a cell surface protein called CD1 that bears an unknown lipidic ligand.

Once the NK T cells bind to CD1, they become activated and begin to secrete a large amount of proteins like interferon-gamma and interleukin-4, which in turn activate helper T cells. The helper T cells then induce specific B cells to unload bursts of soluble antibodies into the bloodstream, and these antibodies ultimately deal with cancerous cells and pathogens.

"These [NK T cells] are the master keys for the regulation of the immune system," says Teyton.

Critical Transfer Protein

Lipid binding to CD1 is not confined to the immune response, though, and endogenous human lipids seem to bind to CD1 as a way of maintaining normal bodily homeostasis.

A few years ago, Teyton was asking how the body loaded natural lipids onto CD1 molecules. He realized that there would have to be another protein inside cells that would transfer the lipid to the CD1 molecule, and so he searched on his computer for possible candidate proteins that could bind to lipids and transfer them onto CD1.

He found a family of genes that encode what are known as lipid transfer proteins, which were already well-characterized because they have been implicated in a number of neurological pediatric diseases. He began investigating whether any of these was the critical transfer protein he sought.

Indeed, one was.

Teyton and his colleagues found that if they removed the gene encoding for the protein prosaposin, they lost all NK T cells. This loss occurred because without prosaposin, the CD1 proteins were never loaded with the lipid, and therefore the NK T cells could not be selected in the thymus of the mutant mice. In addition, using recombinant forms of the saposins molecules, they demonstrated that saposin molecules could efficiently transfer lipids onto CD1d molecules.

Now the researchers are looking at which lipids bind to the CD1 molecules and how they are transported into the cell.


This work was done in very close collaboration with the laboratory of Dr. Albert Bendelac at the University of Chicago.

The research article "Editing of CD1d-Bound Lipid Antigens by Endosomal Lipid Transfer Proteins" is authored by Dapeng Zhou, Carlos Cantu III, Yuval Sagiv, Nicolas Schrantz, Ashok B. Kulkarni, Xiaoyang Qi, Don J. Mahuran, Carlos R. Morales, Gregory A. Grabowski, Kamel Benlagha, Paul Savage, Albert Bendelac, and Luc Teyton and appears in ScienceExpress, the online version of the journal Science on December 18, 2003.

The research was funded by the National Institutes of Health and the Cancer Research Institute.

Jason Bardi | EurekAlert!
Further information:
http://www.scripps.edu/

More articles from Agricultural and Forestry Science:

nachricht New gene for atrazine resistance identified in waterhemp
24.02.2017 | University of Illinois College of Agricultural, Consumer and Environmental Sciences

nachricht Researchers discover a new link to fight billion-dollar threat to soybean production
14.02.2017 | University of Missouri-Columbia

All articles from Agricultural and Forestry Science >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>