NIAID Grantees Receive International Prize For Findings On Immune System

National Institute of Allergy and, Infectious DiseasesFOR IMMEDIATE RELEASE, Tuesday, April 27, 1999, Ellen O'Donnell

Jack L. Strominger, M.D., and Howard Hughes investigator Don C. Wiley, Ph.D., professors at Harvard University and grantees of the National Institute of Allergy and Infectious Diseases (NIAID), have been jointly selected to receive the Japan Prize, a prestigious international award in the fields of science and technology. The prize, given by the Science and Technology Foundation of Japan, recognizes their research isolating and characterizing the three-dimensional structures of certain key molecules (human histocompatibility proteins), complexes and interactions involved in the human immune response. This may lead to new vaccines against tumors and infectious diseases, improvements in transplantation, and better understanding of certain autoimmune diseases.

The two will receive the Japan Prize, which includes an honorarium of 50 million yen (about $440,000), at a ceremony in Tokyo on April 28, in the presence of the Emperor and Empress of Japan.

The prize to Drs. Strominger and Wiley honors a series of accomplishments, including the determination of markers on the surface of most cells of the body, called major histocompatibility (MHC) molecules; the discovery of how MHC molecules bind with another cell component called antigenic peptides, a critical early step in the immune response; and the crystallization and mapping of these structures at the atomic level. NIAID has funded part of the work over the past four decades.

The human immune system is capable of distinguishing its own components from foreign substances or molecules called antigens, which can come from a bacterium, virus or even pollen. In certain cells, MHC molecules recognize fragments of the antigen, bind and present pieces of it as peptides on the surface of a cell. When a T cell, an important type of white blood cell, encounters the MHC-peptide complex on the other cell's surface, it runs a background check and determines if the peptide is part of the body or foreign. If it reads "foreign," the T cell binds to the complex and initiates other steps to protect the body, such as killing the altered cell, and organizing and directing other immune responses such as the release of antibodies.

"In their remarkable research careers, these outstanding scientists have greatly advanced our understanding of the induction and regulation of immune responses," says NIAID Director Anthony S. Fauci, M.D. "By elucidating the structures and processes involved in antigen presentation, they have helped open the door to promising new therapeutic approaches to treating infectious diseases, immunologic conditions and cancers."

Dr. Strominger began studying MHC proteins in the early 1970s. Wondering why the body rejects tissue grafts, he began to investigate transplantation antigens (later renamed MHC proteins), whose genetically determined, distinct polymorphic forms fascinated him. He and his co-workers eventually isolated and separated the two classes of proteins encoded in the MHC complex, an extremely difficult task, and went on to discover their structures and certain features each class shares.

Dr. Wiley collaborated with Dr. Strominger to form these molecules into a solid crystal. Using a technique called x-ray crystallography, they elucidated the crystals' three-dimensional structure at the atomic level. Further, they made crucial discoveries about the interactions of MHC proteins, peptides, T-cell antigen receptors, and other structures and processes.

"Exquisite mechanisms" have evolved in the body, Dr. Strominger says, that result in tolerance to "self" antigenic peptides, while permitting recognition of foreign peptides. However, he notes that the immune system, like all highly tuned systems, is subject to error. Examples of such errors are the development of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and diabetes. An estimated 5 percent of the world's population suffers from autoimmune diseases.

Dr. Strominger is Higgins Professor of Biochemistry at Harvard and a scientific member of the Dana-Farber Cancer Institute, Harvard Medical School. He received degrees from Harvard and the medical school at Yale University. Dr. Wiley is a graduate of Tufts University and holds a Ph.D. from Harvard, where he is the John L. Loeb Professor of Biochemistry and Biophysics. He also is an investigator at the Howard Hughes Medical Institute at Harvard University and The Children's Hospital, Boston. Both scientists have received other important awards, including election to the National Academy of Sciences and the 1995 Albert Lasker Basic Medical Research Award. Over 50 winners of the Lasker Award have gone on to receive Nobel Prizes.

"I'm thrilled about the Japan Prize," Dr. Wiley said. "I think it recognizes research that was done over a period of about 15 years which involved many grad students and postdoctoral fellows." He especially cited Pamela Bjorkman, Ph.D., who solved the structure of the class I MHC molecule and is now a professor and NIAID grantee at the California Institute of Technology. Dr. Strominger commented, "Prizes are fun, but the real thrill is doing the work and seeing the result." He also cited those in his lab who have worked with him over a period of almost 30 years.

Two Japan Prizes are awarded each year. In addition to Drs. Strominger's and Wiley's shared prize, the other has been presented to W. Wesley Peterson, Ph.D., a professor of information and computer sciences at the University of Hawaii at Manoa, for his research in digital communications error control.

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as AIDS, malaria, tuberculosis, asthma and allergies. NIAID is an agency of the U.S. Department of Health and Human Services.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.