Editor's Note: Science Scan is a roundup of recently published biotechnology-relevant research.
Natural killer T cells (NK T) are key players in the mammalian immune system. They have been implicated in autoimmune diseases, such as diabetes mellitus, as well as in cancer - although researchers have not yet discerned precisely how. NK T cells are unusual in that they fall somewhere between innate and adaptive immunity. They arise in the thymus, (source of the word T cell') and as mature cells stimulate an adaptive immune response. As such, they regulate a range of disease states, including diabetes, cancer and pathogenic infections.
Like other T cells, these express T-cell receptors (TCR). Classical immune recognition involves a process in which variable TCRs recognize various protein fragments - pieces of proteins from foreign pathogens, for example. They are attracted to the attention of the immune system by "antigen-presenting cells" via a molecule called the major histocompatibility complex (MHC). Like burglar alarms, MHC cells warn the immune system that a pathogen is invading.
However, NK T cells also express the "NK" innate immune cell receptors, along with the adaptive ones. Thus, they might have the ability to "see" some of the lipids that bacteria such as Mycobacterium tuberculosis (cause of TB infection) display on their outer surface. NK T cells become activated when they bind to a cell-surface protein called CD1. Once the NK T cells bind to CD1, they become activated and begin to secrete a large amount of cytokines - e.g. interferon-gamma and interleukin-4 - which in turn activate helper T cells. Those then induce specific B cells to unload bursts of soluble antibodies into the bloodstream. The antibodies ultimately deal with cancerous cells and infectious pathogens. 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.
Associate Professor Luc Teyton at The Scripps Research Institute in La Jolla, Calif., has discovered a family of proteins that connect the immune system to the bodily lipids - the fat molecules that are a major building block of the human body. He is lead author of a Sciencexpress paper titled "Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins."
A few years ago, Teyton was wondering 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. He and his co-authors found a family of genes that encode lipid-transfer proteins. They were already well characterized because they had been implicated in a number of neurological pediatric diseases. The team began investigating whether any of those was the critical transfer protein they sought. Indeed, one was: Teyton found that without a protein called saposin, the CD1 proteins were never loaded with the lipid, and therefore the NK T cells could not be selected in the thymus of their experimental mutant mice.
Hong Kong, Hotspot Of Global SARS, Pits Two Major Facilities Against Each Other's Cause
Severe acute respiratory syndrome (SARS) is a global health concern. Hong Kong has been one of the greatest SARS-afflicted cities in the world. By May 15, the local case number had mounted to 1,703, and a quarter of those were part of two large epidemiological outbreaks. The first took place at Hong Kong's Prince of Wales Hospital, into which 156 SARS cases were reported between March 11 and March 25. The second, at Amoy Gardens, occurred where 321 infected residents were admitted by April 15. That is a densely populated housing complex of 10 33-story apartment blocks. The two outbreaks were marked by the rapid spread of SARS among individual patients. Yet certain features in the disease differed from case to case.
The possibility that two different viral strains were responsible for the outbreaks at the two facilities are disputed by authors of a research letter in The Lancet, dated Nov. 29, 2003. Its title: "No significant genetic difference in viruses responsible for two major Hong Kong SARS outbreaks." The apparent increase of diarrhea (73 percent, compared with 20 percent), admission to intensive care (32 percent, compared with 23 percent) and death (13 percent vs. 4 percent) among the Amoy Gardens units had resulted in the theory that the two viruses responsible had different genetic structures.
African Clawed Frog Renders Animal Gestation In Mouse Model Visible, Aping Human Condition
A single gene named shroom (short for mushroom) apparently kicks off a critical step in development of the early embryo - formation of the brain and spinal cord. That might offer a way to screen for fetal spinal defects such as spina bifida (an exposed spinal cord). Neural tube defects, as well as anencephaly (absence of a complete brain), are among the commonest serious birth defects in the United States. While its incidence has declined in the U.S., thanks to efforts encouraging pregnant women to consume folic acid (vitamin B), some 30 percent of neural tube defects appear to have a genetic etiology unrelated to folic acid deficiency.
Reporting in the Dec. 16, 2003, issue of Current Biology, researchers at the University of California at Berkeley and the University of Pittsburgh established that activation of a lone gene (none other than shroom) triggers specific cells in the growing embryo to bend. That initiates a curling of tissue into a closed neural tube that eventuates in spinal cord and brain. The joint paper's title is "Shroom induces apical constriction and is required for hingepoint formation during neural tube closure."
Though conducted in African clawed frog embryos (Xenopus laevis), the experiments have implications for all vertebrates, including humans. Despite the large number of genes involved in proper neural tube closure, little or nothing is known about the function of those genes because mice embryos develop inside their mother's uterus, where it's impossible to watch the closure process. The African frog simulates and reveals the human condition.