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 Back to Nature: Palm oil plantations are being turned back into protected rainforest
21.03.2019 | Forschungsverbund Berlin e.V.

nachricht The inner struggle of the evening primrose: Chloroplasts are caught up in an evolutionary arms race
14.03.2019 | Max-Planck-Institut für Molekulare Pflanzenphysiologie

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: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>