Ongoing Collaboration Between TSRI and Princeton Scientists Reveals Details of Natural Killer T Cells

By Jason Socrates Bardi

In the latest of what has become a series of collaborative studies between two laboratories on opposite coasts, Associate Professor Luc Teyton of The Scripps Research Institute (TSRI) and Albert Bendelac of Princeton University further characterize an immune cell, known as a natural killer (NK) T cell, or "NK1.1 T cells," which regulate other immune cells.

In the current study, the researchers provide a detailed look at the maturation of the NK1.1 T cell lineage, following its migration from its early precursor days in the thymus to its differentiation in various tissues in the body.

"We are basically trying to understand how the NK1.1 system works," says Teyton, who adds that the long-standing collaboration has its roots in Paris, where Teyton and Bendelac knew each other as students before both came to the United States.

The NK1.1 T cells are unusual in that they fall somewhere between innate and adaptive immunity. These cells arise in the thymus. 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. However, NK1.1 T cells also express the "NK" innate immune cell receptors and may have the ability to see some of the lipids that many bacteria display on their outer surface. This NK receptor recognizes the CD1 receptor, which is associated with the major histocompatability complex on antigen presenting cells, which are like the buglers that warn the immune system that a pathogen is invading.

NK1.1 T cells bind to a cell surface protein called CD1 that bears an unknown lipidic ligand, one focus of Teyton and Bendelac's current investigations.

Once the NK1.1 T cells bind to CD1, they become activated and begin to secrete a large amount of the protein interleukin-4, which in turn activates 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.

One of the toughest challenges in studying NK1.1 T cells is simply expressing and purifying biologically active CD1 receptors. This task is almost impossible in bacterial expression systems. So Teyton expresses the molecules in Drosophilla cells and purifies them as empty, fully folded proteins from culture supernatants. They are subsequently multimerized and loaded with antigenic lipids to make them react with the T cell receptor of NK1.1 T cells.

In the current study, Teyton made these reagents to look specifically at the thymic development of these cells.

"We also expressed NK1.1 soluble T cell receptors to examine their binding to CD1 molecule," says Teyton. He adds that these studies are the preliminary work that will lead to the determination of TCR/CD1 complex structures. The same approach was used in 1996 by Teyton and TSRI Professor Ian Wilson of the Department of Molecular Biology, when they crystallized the TCR and TCR/MHC complex and solved their structures.

The article, "A Thymic Precursor to the NKT Cell Lineage," is authored by Kamel Benlagha, Tim Kyin, Andrew Beavis, Luc Teyton, and Albert Bendelac and appears in the March 14, 2002 issue of the journal Science





mCD1d-aGC tetramer

NK1.1 mAb


Identification of NK1.1 cells in 7 wk C57BL/6 mouse lymph nodes by immunocytochemistry. Staining with CD1-aGC tetramers (top) superimposes with anti-NK1.1 staining (center). Observation was carried out by Confocal microscopy (63x (oil) lens, 1x Zoom).