Crucibles in the cell – special issue: 1994

Crucibles in the cell – special issue: 1994 – the Year in Science

Mark Caldwell

Back in van leeuwenhoek’s day, when the microscope was a novelty, living cells defined the limits of little. It was inconceivable to biologists that they would one day intimately study structures within the cell, structures so small that beside them the cell looms like a swollen, lumbering giant.

Ah, such shortsighted visionaries: these days biologists can glimpse tiny organelles under powerful electron microscopes. Of course, until recently that was just about all they could do: many cellular structures were simply too small to get hold of or get into and thus were difficult to characterize. Now new tools are changing that. Biologists can tell which organelles they’re dealing with by sending out biochemical probes to detect the cell’s constituent proteins. They can even show how the organelles work. And those workings often prove to have importance out of all proportion to the size of the worker.

One illustrative find this past year seems to have solved a major riddle of the immune system by revealing a key step in the way it detects foreign invaders. Last May researchers from the United States, the Netherlands, and Scotland announced that they’d identified a brand-new organelle – a submicroscopic crucible secreted deep inside one particular type of immune cell. Tiny though it is, the organelle appears to be responsible for assembling one of the immune system’s most essential components: a tight little bundle of proteins that trigger the complex cascade of events that ultimately protect you from disease.

Immunologists have known for years that when a foreign invader, or antigen, first enters the body, it’s swallowed by an immune-system sentinel: a white blood cell called a B lymphocyte. Once it has engulfed the antigen, the B cell minces it into bits of protein, or peptides, which it then brandishes on its surface as a signal to other immune cells. As the B cell then courses through the bloodstream, the immune system’s attack cells, alerted by the warning signals, spring into action. But there’s a catch: the attack cells respond to a foreign peptide only if it’s displayed in the clutches of a nonforeign protein called HLA in humans, and MHC Class H in the mice that immunologists usually study. These proteins are distinctively yours, marking you as yourself. Your immune system, after all, needs to know who’s who; it doesn’t want to attack everything indiscriminately, only foreigners that it perceives as having contaminated you.

What immunologists have not known, however, is just where in the B cell foreign antigens are broken down, and how the resulting peptides are combined with MHC to form a “complex” – a tight little bundle that squishes out onto the cell surface like a wad of bubble gum. Now it’s clear that the hidden workshop is the newly discovered organelle of 1994. Thanks to their probes, the researchers were able to track both the antigen arriving in a cell and the MHC protein produced in the cell’s nucleus and to see that the two paths merged at the hitherto unknown structure.

Cell biologist Sandra Schmid of the Scripps Research Institute in La Jolla, California, has dubbed the organelle the CPL, for compartment for peptide loading.” She describes what goes on inside the CPL as a dynamic, multistep process, like cooking. It’s like a little pot of ingredients simmering on a stove,” she says. Gradually self and nonself proteins are reduced and stirred into a new combination that’s irresistible to the immune system’s attack cells.

Of course, many questions about this process remain. But immunologists now know just where to search for the rest of the answers.

COPYRIGHT 1995 Discover

COPYRIGHT 2004 Gale Group