The antibody, called 2G12, was isolated about a decade ago from one of the rare HIV-positive individuals whose body is able to successfully combat the virus. Scientists at the Scripps Research Institute worked with an international team to determine the 2G12 antibody structure by diffracting X-rays from crystals of 2G12.
The structure reveals an unexpected intertwining of the antibody's two chains, the extensions that grab hold of the AIDS virus. Researchers also uncovered how the 2G12 antibody neutralizes HIV by binding to sugars on the surface of the virus. The immune system usually will not attack these sugars because they are made and attached to the AIDS virus by human cells; the immune system usually accepts them as if they are part of the body.
The structure of the 2G12 antibody could provide scientists with a template to design an antigen that would trigger the body to produce 2G12. Antigens are molecules that the immune system recognizes as foreign; they stimulate the immune system to produce antibodies to combat invading microbes. The scientists believe that it might be possible to design an antigen to entice the body to produce 2G12. Such an antigen could be the basis of a vaccine against HIV.
This research was led by Ian Wilson, D. Phil., and Dennis Burton, Ph.D., both of the Scripps Research Institute, as well as scientists from Florida State University, the University of Oxford and the University of Agriculture in Vienna, Austria.
NIH's National Institute of General Medical Sciences supports Wilson through a program that brings together crystallographers, chemists and biologists to determine the detailed, three-dimensional structures of potential HIV drug targets.
Contact: Linda Joy
NIH/National Institute of General Medical Sciences