Estimating the Probability of Polyreactive Antibodies Disabling a Gp41 Trimer after T Cell-HIV Adhesio

IAM-PIMS Distinguished Colloquium
October 22, 2012 10:00 pm

Speaker:  Dr. Byron Goldstein, Los Alamos National Laboratory, Los Alamos, New Mexico

URL for Speaker:

Location:  LSK 460

Intended Audience:  Public

A small number of broadly neutralizing monoclonal antibodies (mAbs) have been isolated from HIV-1 infected individuals. A subset of these recognizes epitopes in the membrane proximal external region (MPER) of gp41 that are transiently exposed during viral entry. The best characterized of the MPER binding mAbs, 4E10 and 2F5, are polyreactive, binding to both the viral membrane and their epitopes in the MPER. We present a model that allows us to calculate, for a given antibody concentration, the probability that during the transient period when the epitopes in the MPER are exposed, a trivalent gp41 will be rendered incapable of completing the fusion process. For a series of neutralization experiments using different mAbs, but the same virion and target cells, the model predicts a way to plot the data so all experiments fall on a universal curve. The data plotted in this way indeed lie on a single curve, suggesting the model has captured a major feature of neutralization experiments. However, as I will explain, comparison of model predictions with experiment indicates that the model is missing some process or processes that influence neutralization.

Byron Goldstein has been a member of the Theoretical Biology and Biophysics Group at Los Alamos National Laboratory since 1975. His focus has been on cell surface receptors that play key roles in the immune response and how they mediate cell signaling. For a number of years he has been involved in building a detailed predictive model of the signaling cascade triggered during an allergic reaction when an allergen binds to IgE on the surface of mast cells and triggers the release of histamine and other mediators of anaphylaxis. He received an NIH MERIT award in 2003 and was made a Laboratory Fellow in 2005. This summer he received the q-Bio Award “For pioneering studies of cell surface receptors and signaling systems and for being a visionary q-biologist even before q-bio was fashionable.”