New technique redirects immune response - C&EN Global Enterprise

Apr 1, 1991 - A technique by which substances that are normally immunologically silent can be made vulnerable to attack by the immune system has been ...
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sue of Fusion Technology [19, 313 (1991)]. He has read the paper of Miles and Bush (no relation) and finds their results 'Very encourag­ ing." In any case, the Naval Weapons Center researchers do not have the data necessary to implicate any spe­ cific nuclear reaction. "We don't know what the physics is," Ben Bush says. Nobody really does. Hoffman says as "cold fusion" investigations con­ tinue around the world, more and more evidence is being uncovered that "some anomalous nuclear pro­ cess" can occur in metal-deuterium systems. The apparent absence of 3 He and other evidence suggests that conventional D-D fusion is not occurring. But a different nuclear process that produces bursts of neu­ trons, for example, seems more like­ ly. "And we're looking for other phenomena that may be associated with it, such as helium-4 or charged particles," he says. The Miles and Bush paper is sig­ nificant, at the very least, because it is the first to claim definitive obser­ vation of helium production in a "cold fusion" cell. The paper was ac­ cepted for publication in the Journal of Electroanalytical Chemistry (JEC) af­ ter its editor, electrochemist Roger Parsons of the University of South­ ampton, reviewed it and decided it was suitable. Submitted as a "pre­ liminary note," the paper did not have to be—and was not—scruti­ nized by other reviewers. In fact, Bush remarks, acceptance of a paper by fiat of the editor is "the most prestigious way" to get a paper pub­ lished in a journal. Parsons tells C&EN that JEC has published some 20 to 25 papers on cold fusion since Pons and Fleischmann published their original re­ port on that subject in the same jour­ nal. The subsequent papers have been about equally divided in pre­ senting either positive or negative results on cold fusion. "There isn't a definitive answer at the moment," Parsons concludes. But Robert Bush of Cal Polytech­ nic is somewhat more upbeat: "Even though Pons and Fleischmann made some errors in interpreting their data," he says, "they weren't totally wrong." D

New technique redirects immune response A technique by which substances that are normally immunologically silent can be made vulnerable to at­ tack by the immune system has been developed by chemists at the Uni­ versity of California, Berkeley. The scientists are now evaluating the concept in vivo as a potential new approach to immunotherapy. Berkeley chemistry professor Pe­ ter G. Schultz, who directed the re­ search, points out that, while the im­ mune system is remarkably efficient in protecting vertebrates, microor­ ganisms, viruses, and other patho­ gens have evolved a number of strategies for evading neutralization by the immune system. For example, viral coat proteins can have high mutation rates; for such viruses, the immune system " s e e s " a continuously changing pathogen. Coat proteins also can be glycosylated in patterns that mimic glycosylation patterns of the organ­ ism, thus rendering them "invisi­ ble" to the immune system. Addi­ tionally, conserved regions of the coat protein may lie in canyonlike structures that are inaccessible to an­ tibody combining sites. And there may be only transient exposure of highly antigenic, conserved sites during uncoating, a process that oc­ curs as a virus is infecting a cell. Schultz points to the human im­ munodeficiency virus (HIV), the cause of AIDS, as one that very likely harnesses all four of these strategies for evading immune surveillance. Schultz and Berkeley graduate student Kevan M. Shokat have de­ vised a way to redirect the immune system's powerful memory response toward substances not normally rec­ ognized as foreign [/. Am. Chem. Soc, 113, 1861 (1991)]. In research sup­ ported by the Department of Ener­ gy, highly immunogenic antigens were tethered to ligands that bind selectively to conserved sites on a target protein. Noncovalent binding interactions result in the introduc­ tion of this new antigen onto the target's surface, thereby tagging the target for recognition and neutral­ ization by the immune system. Schultz laughingly refers to the technique as "painting bull's eyes on proteins."

Schultz: paints bull's eyes on proteins One of the proteins the chemists targeted was the HIV coat glycopro­ tein, gpl20. To do this, they attached dinitrobenzene (DNP) to a soluble form of the Τ lymphocyte cell sur­ face antigen CD4. The first step in HIV infection of a T cell is the bind­ ing of gpl20 to CD4. It is widely thought that the conserved region of gpl20 that interacts with CD4 is in a deep, immunologically inacces­ sible cleft on the glycoprotein. For reasons that are not under­ stood, about 1 to 2% of all naturally occurring human antibodies recog­ nize the DNP group. Anti-DNP an­ tibodies are recognized by Clq, the first component of the complement cascade, which is responsible for de­ stroying cells or viruses on which immune complexes form. Schultz points out that other known antigens such as peptides and sugars could be used as an alternative to DNP. Schultz and Shokat demonstrated that the CD4-DNP construct binds to gpl20, that the bound CD4-DNP is recognized by anti-DNP antibod­ ies, and that these bound, anti-DNP antibodies subsequently bind Clq. They also showed that DNP teth­ ered to biotin, which binds to the protein streptavidin, marks that pro­ tein for binding by anti-DNP anti­ bodies. The ultimate hope is that such an approach will allow development of an agent that will coat, for example, April 1, 1991 C&EN

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Science/Technology the HIV particles in an infected individual with DNP. This would make the virus a target for the large number of anti-DNP antibodies the individual already possesses. If the idea w o r k s , no n e w i m m u n i t y would be required to stimulate the immune system to attack HIV. This is highly advantageous in the case of viral infections such as AIDS that impair the immune system. Schultz says the research "suggests that it may be possible to direct a neutralizing antibody—ideally antibodies already present in the sera— against any cellular or viral surface for w h i c h a selective ligand is known. Such ligands might come from screens of recombinant libraries, collections, or fermentation broths/' The CD4-DNP construct is currently being tested in cultures of HIV-infected lymphocytes. Schultz is also seeking other gpl20-specific ligands with which to test the technique. Rudy Baum

Hubble Telescope to monitor Mars' changes The National Aeronautics & Space A d m i n i s t r a t i o n ' s H u b b l e Space Telescope is beginning a long-term program to monitor seasonal and annual changes in the planet Mars' surface and its active atmosphere. Comparison of images obtained at different times is expected to increase understanding of weather p a t t e r n s , climate, a n d surfacechange processes on the red planet, and help prepare for future manned and unmanned exploration. The program is made possible by the sharp images of Mars that Hubble's wide field and planetary camera is obtaining. Preliminary observations already have yielded the sharpest images of Mars ever taken from Earth's vicinity. The images clearly show atmospheric features, and surface and topographic details as small as 50-km across. Ground-based telescopes, looking

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State-of the-Art 3-Day Symposium on

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April 1, 1991 C&EN

This color image of Mars is a composite of images obtained through red, green, and blue filters with the Hubble Telescope's planetary camera. Computer processing partially overcame the blurring effects of spherical aberration in the telescope's primary mirror. At the time, Mars was 85 million km from Earth, with its north pole near the center of the bluish clouds at the top. The large, dark shark's fin-like feature, called Syrtis Major Planitia, is thought to be caused by coarse, dark sand deposits, possibly from weathering of volcanic rock through the distortions produced by Earth's atmosphere, cannot do such continual monitoring. Most also cannot resolve Mars' features smaller than 600 to 1000 km, although 150 km has been achieved. The team undertaking the program includes Philip James, University of Toledo; Steve Lee and R. Todd Clancy, University of Colorado; Ralph Kahn and Richard Zurek, Jet Propulsion Laboratory; Leonard Martin, Lowell Observatory; and Robert Singer, University of Arizona. Hubble also is providing new data on the abundance of ozone in Mars' atmosphere. Because it is located in space, Hubble can observe Mars in ultraviolet light, which normally is absorbed by ozone in Earth's atmosphere. By comparing images of Mars at different wavelengths, the team can measure absorption of ozone in the Martian atmosphere, especially over the dry polar regions. Apparently, water vapor initiates chemical reactions that remove ozone from the Martian atmosphere. Team scientists hope to use the ultraviolet data to monitor the amount of water, as well as ozone, in Mars' atmosphere. Richard Seltzer