PROJECT SUMMARY
Mammals have evolved several antibody isotypes capable of engaging distinct response pathways upon
subsequent recognition of antigen. Immunoglobulin E (IgE) is an antibody isotype highly specialized to rapidly
and potently activate Type II effector cells. The deleterious role of IgE in allergic disease has been well-
described in the literature extending back to the early 20th century. However, the roles of IgE in homeostasis
and in host protection from disease remain poorly understood.
One approach to understanding the functional role(s) of antibody isotypes is through identifying targeted
antigens. Reactivity profiling has been performed for all antibody isotypes except for IgE and has been
informative in establishing the tissue sites, effector pathways, and functional consequences of antigen
recognition by specific antibody isotypes. The antigenic targets of IgE have not been broadly characterized to
date largely due to the difficulty in obtaining sufficient antibody quantities for testing. We created a genetic tool
to both extend the half-life of IgE and to facilitate IgE purification, enabling high-throughput reactivity
screening. Preliminary data for this proposal showed that during homeostasis and after infectious challenge,
IgE and IgG recognized distinct sets of antigens. Some reactivities unique to the IgE antibody pool were
conserved under all tested conditions, suggesting that these antigen:antibody interactions are an important
component of fundamental IgE biology. Additional data demonstrated that homeostatic IgE had a profound
influence on the host response to acute inflammatory challenge, and that this influence was antigen-
dependent. We propose to fully resolve IgE reactivities in homeostasis (Aim 1), in relevant genetic and
environmental contexts (Aim 2), and ultimately to contextualize IgE effector function(s) within the host
response to acute inflammatory perturbation (Aim 3).