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 research recovers nutrients from seafood process water
31.10.2018 | Chalmers University of Technology

nachricht Plant Hormone Makes Space Farming a Possibility
17.10.2018 | Universität Zürich

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: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Epoxy compound gets a graphene bump

14.11.2018 | Materials Sciences

Microgel powder fights infection and helps wounds heal

14.11.2018 | Health and Medicine

How algae and carbon fibers could sustainably reduce the athmospheric carbon dioxide concentration

14.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>