|Dendritic cells in the skin (Langerhans cells) form a dense network of “sentinels” that act as first line of defense of the immune system.1|
What happens when a pathogen invades us? Well, lots of things happen, of course. Early on, there are innate immune responses; generic pathogen-like aspects of the pathogen trigger a relatively stereotyped immune response. Parts of this innate immune response then connect the pathogen features to the adaptive immune response (T cells and B cells), and in a few days there should be a much larger and more focused (pathogen-specific) immune response.
This link between the innate and the adaptive immune response is most often made by dendritic cells (DC). DC hang out in tissues all over the body, forming a net that constantly filters stuff in the tissues (see the image to the left). Almost all the time (one hopes) these DC don’t run into any pathogen signatures; and in that case, they just continue to hang out and filter some more. When a DC does run into something that’s associated with a pathogen (such as, say, lipopolysaccharide, LPS, a part of some bacterial cell walls) then the DC changes and enters a new program designed to efficiently interact with T cells.
There’s been no obvious reason to suspect that antigen presentation is connected to movement of the dendritic cell. But a paper in today’s issue of Science2 shows that in fact the two are tightly linked, because the same protein helps regulate both of them. This protein is the invariant chain (also known as Ii), and it’s been known for years that it’s important in antigen presentation; the details of that are well worked out. The new, and really surprising, finding is that Ii also helps control movement of dendritic cells (and probably other cells, such as B cells, that also have Ii), by interacting with myosin II. The authors show that Ii acts as a brake on DC movement, and this brake is released when (as a part of its normal antigen presentation function) Ii is partially destroyed.
The use of common regulators for Ag processing and cell motility provides a way for DCs to coordinate these two functions in time and space. In immature DCs that patrol peripheral tissues, the periodic low motility phases induced by Ii may enable DCs to efficiently couple Ag uptake and processing to cell migration, facilitating the sampling of the microenvironment. 2
The concept makes sense; the DC would want to look more closely for antigens in an area they’d just arrived in, rather than in somewhere they’ve already sampled for a while. One interesting implication, I think, is that antigen presentation, like the movement that they show, may be episodic, happening in bursts rather than in a continuous conveyer belt. We already knew that the conveyer belt was jerky on a larger scale, but I think this suggests that it’s on and off on a much finer scale than has been previously shown (as far as I know). I have some interesting data on a different type of antigen presentation that would fit with this model, so I’ve been wondering for a while about looking for jerkiness in antigen presentation anyway, and maybe this reinforces that notion.
By the way, the paper has some cute movies of dendritic cells in little runways, chugging down the lines like little trains, including the DC’s occasional stops and reversals like a train that’s passed the passenger loading area and has to back up.
- Tolerogenic dendritic cells and regulatory T cells: A two-way relationship. (2007) Karsten Mahnke, Theron S. Johnson, Sabine Ring and Alexander H. Enk. J of Derm Sci 46:159-167 doi:10.1016/j.jdermsci.2007.03.002 [↩]
- Gabrielle Faure-André, Pablo Vargas, Maria-Isabel Yuseff, Mélina Heuzé, Jheimmy Diaz, Danielle Lankar, Veronica Steri, Jeremy Manry, Stéphanie Hugues, Fulvia Vascotto, Jérôme Boulanger, Graça Raposo, Maria-Rosa Bono, Mario Rosemblatt, Matthieu Piel, Ana-Maria Lennon-Duménil (2008). Regulation of Dendritic Cell Migration by CD74, the MHC Class II-Associated Invariant Chain Science, 322 (5908), 1705-1710 DOI: 10.1126/science.1159894[↩][↩]