Donor antibodies, administered intravenously or subcutaneously, make up a commercial product used to treat both immunodeficiencies and inflammatory or auto-immune diseases.
These preparations contain a complex mix of antibodies against glycans, the carbohydrate molecules on the outsides of cells, a Jan. 7Â paper in Science Translational Medicine reveals.
At first glance, the findings are remarkable because:
A. Immunologists have long thought that carbohydrates, by themselves, are not good at provoking the immune system. (The assumption was: you need some protein for antigen presentation and getting T cells interested.) The data shows exceptions to the rule.
B. Some of the antibodies react against human carbohydrate structures. Instead of attacking them in an auto-immune fashion, they may actually be blocking viruses or bacteria from using those structures as gateways to infection.
The lab of Stephan von Gunten at the University of Bern collaborated with the National CenterÂ for Functional Glycomics led by biochemists Rick Cummings and David Smith at Emory to analyze the spectrum of carbohydrate structures bound by donor antibodies. Read more
Pigs are natural hosts for influenza viruses that can infect humans, in particular the 2009 and, going way back, 1918 H1N1 flu strains. So to understand how influenza infections spread in the body, biochemists and virologists look at pigs.
Biochemistry chair Rick Cummings’ group has a paper in PNAS this week examining the carbohydrates or glycans on the surfaces of pig lung cells, using their “shotgun glycomics” library approach. MMG graduate student Lauren Byrd-Leotis is the first author.
“The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis,” the team reports.
Biochemists Rick Cummings and David Smith have a paper in Journal of Biological Chemistry describing antiviral sugar molecules present in human milk. The first author is postdoctoral fellow Ying Yu.
Cummings and Smith are pioneers in the field of glycomics, studying the sugar molecules that decorate our proteins and coat our cells. They have found that human milk contains specialized glycans (carbohydrate linked to other molecules such as protein or lipid) that bind to influenza virus. This is separate from, and a supplement to, the adaptive immunity of antibodies and vaccines.
â€œThe anti-flu glycans are not induced to our knowledge, but are part of a naturally occurring â€˜liquid innate immune systemâ€™ in human milk,â€ Cummings says. â€œWe’re very excited about this, and the availability of the human milk glycome in printed microarray formats will now allow screening for glycan binding to a wide variety of infant pathogens. This came from a single donor, so as to not complicate the matter yet, but work in progress shows that glycans from other donors have many related but also different glycans.â€
He adds that his lab is finding that the glycans in human milk are different overall in complexity and makeup from those in other mammals.
Smith hypothesizes that the glycans may be functioning as “decoy receptors,â€ interfering with the molecules on the surfaces of human cells that viruses use to gain access.
Posted on November 20, 2012