NEWS Nobel goes to T-cell pioneers whose work 'changed face of '

London. The 1996 Nobel prize for physio­ i without harming healthy cells. logy or medicine has been awarded to two They also knew that the complicated and immunologists for a pioneering discovery, intricate job of protecting the body from made more than two decades ago, of the infection was carried out by T- and B-lym­ way in which the recognizes phocyte cells. Researchers had determined -infected cells. that produced by B- The award has been made to Peter C. could recognize and eliminate microorgan­ Doherty, adjunct professor of pathology and isms, such as bacteria. While it was known paediatrics at the University of Tennessee how T-cells could reject tissue transplants College of Medicine, and Rolf M. Zinker­ following recognition of molecules known as nagel, head of the institute of immunology major histocompatibility , how at the University of Zurich in Switzerland. It these cells recognized virus-infected cells comes as belated recognition for research was unclear. that had an immediate impact on immun­ Jonathan Howard, a geneticist at the ology, and has since paved the way for University of Cologne, says that Doherty improved understanding of infectious dis­ and Zinkernagel clarified the role of histo­ eases and chronic inflammatory conditions, compatibility antigens by using real such as diabetes and multiple sclerosis. and set the agenda for the next ten years of The Nobel prize is the second award to research. The breakthrough have been won by the scientists in consecu­ came when they carried out Restriction of in vitro T cellamediated tive years for a discovery that was initially cytotoxicity in lymphocytic chorio,. experiments designed to published in April 1974 (see Nature 248, 701; meningitis within a syngeneic or investigate how T-lympho­ semiallogeneic system 1974) and built upon in October of the same fuc:KNT experiml'nts1-• indicdc t hat IIOO~rfl.lion between cytes protect mice against \hyn:ma derived lrmphoeyt~ (T celb} • nd ,ntibody-formiog year (see Nature 251, 547; 1974). They won cell prtcuN!Ors (B cells) is remicted by the H-2 gene com­ infection from a virus able to plex. Helper activity in vivo operate11 only wbl'!I T cells and the 1995 Albert Lasker Medical Research B tt;D11 share ftt. l~st- ol'le set .of H-2 antigmic sr,ecificities. cause meningitis. Eriden~ is presmtcd here t hat ·thelnteraction or cytotoxic Award for the same work - reinforcing its Double act: Doherty (left) T cells with other somatic ce]!i,1 huddinFi lymphoeytic Mice were infected with choriomeningitis (LCM) vims i9 simil11rly re,,t ricted. reputation as a Nobel 'precursor'. and Zinkernagel, pictured Both the cytotoxic aa,ay used and the cbaraeterist-ice of the virus and developed the cells invo!ved have been dt'!!cribed previously•..,_ Briefly, in 1983, and the 1974 monolayers of C3H moUl!{) fibroblastll (L cells) are grown Their peers were quick to congratulate in plaEtic tis.'lue culture trays, infected with i-. high multi­ virus-killing T-lymphocytes. Nature paper in which they plicity of Lhe WE.3 strain of LCM virU!I aod t he cells labelled both scientists as worthy winners who should with " Cr and o,·erlaid (40:1) with the spleen ceU prepara,. But, unexpectedly, the scien­ set out the crucial piece of tested. Supc t:1nt~ a!'fl r ovN.I betwoo 15 .and have been recognized by the Nobel academy Nobel-winning research. nd % • Be '. R ea tists found that these T-lym­ earlier. "It's about time," says Polly phocytes were unable to kill Matzinger, an immunologist at the National future research into the structure and bio­ virus-infected cells from other strains of Institutes of Health in Maryland. The chemistry ofT-cell immunology. mice, demonstrating that an individual research, she adds, "changed the face of One immunologist, who performed mouse's T-cells remain ineffective unless immunology. [The award] is wonderful". important follow-up experiments, says the they can also recognize the major histocom­ Hidde Ploegh, professor of biology at the prize is "absolutely terrific" news. "I am very patibility antigens of the infected cells. Massachusetts Institute of Technology, says lucky to have been totally inspired by their The findings immediately opened up that "there had never been any question work," says Alain Townsend, professor of several doors to research into the ability of about the importance of this landmark dis­ immunology at the John Radcliffe Hospital, the body's immune system to recognize and covery", which provided the direction for Oxford, and author of research in the react to microorganisms other than viruses. immunology of the influenza virus in the Further research using a range of molecular early 1980s. "I used to refer to Rolf [Zinker­ tools has since confirmed Doherty and Rise in US research nagel] as the Bach of immunology." Zinkernagel's original models, and has Doherty was born in 1940 in Australia, added important structural detail to their spending approved where he completed his masters degree. In more general picture. Washington. Spending by the US govern­ 1970 he completed a PhD at the University Immunologists now know more about the ment on research and deve lopment will of Edinburgh in Scotland, and joined the body's histocompatibility antigens, whose grow substantially next year for the first John Curtin School of Medical Research in recognition by T-cells is important for eradi­ time in four years, rising from $71 billion Canberra two years later. cating viruses. They have worked out that to $74 billion. The 4.1 per cent increase Zinkernagel was born in Switzerland in T-cells recognize a small part of the invading is contained in spending bills hurriedly 1944. He completed his MD thesis at the virus - a peptide - that sticks to the body's agreed by Congress and President Bill University of Basel in 1970, and was still a histocompatibility antigens. Such research Clinton early last week. postgraduate research student, not yet has important implications for the develop­ According to an assessment by the having completed his PhD, when he submit­ ment of vaccines. American Association for the Advance­ ted with Doherty the Nobel-winning "This Nobel prize is very appropriate," ment of Science, basic research will fare research to Nature in December 1973. says Jonathan Sprent, an immunologist at less we ll than applied research and Immunologists at the time knew that the Scripps Research Institute, La Jolla, development, with an overall increase of cells were capable of destroying California. "So much of immunology is 2.7 per cent. D foreign, invading, microorganisms as well as based on what they [Doherty and Zinker­ the body's own infected cells, but somehow nagel] did." Ehsan Masood & Ursula Weiss NATURE · VOL 383 10 OCTOBER 1996 465

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