This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is only a limited understanding of the mechanisms involved in the developmental course of food allergies. To effectively prevent or reverse the progression of food allergy, immune interventions will be needed. Furthermore, it is likely that successful strategies will need to be directed to those persons at identifiable risk (e.g., who have biomarkers associated with development of peanut allergy). This NIH (NIAID) sponsored multi-center (5 sites) observational study will investigate the developmental immunology of peanut, egg and milk allergy in a cohort of milk or egg allergic children who are at risk for peanut allergy. We will recruit 400 infants (approximately 80 at Mount Sinai) with milk or egg allergy and approximately 250 sibling controls (approximately 50 at Mount Sinai) for genetic and immunological studies. Enrolled infants will be evaluated over a 4.5 year period during which time we predict that approximately 20% will develop clinical peanut allergy and 25-50% will experience resolution of egg or milk allergy. We will perform directed immune testing (T cell studies, humoral studies), explore candidate genes that may influence food allergy (toll like receptor polymorphisms) and evaluate environmental exposures and diet that may influence outcomes. This strategy should enable us to delineate, compare and contrast biological markers and immunologic changes associated with the development of peanut allergy and loss of egg and milk allergy while simultaneously evaluating important clinical and environmental influences likely to account for the recent alarming rise in these allergies. Hypotheses to be tested include: The development and persistence of clinical peanut allergy (non-resolution of egg/milk allergy) is associated with: the development of an allergen-specific, Th2- skewed T cell phenotype; a decrease in the T regulatory phenotype of antigen-activated peripheral CD4+ T cells; development of an epitope-specific IgE antibody profile that is distinct from persons without clinical allergy; Toll-like receptor (TLR) Polymorphisms and related genes that impair responsiveness to TLR ligands; Early exposure to allergenic proteins (via breast milk or oral exposure) or homologous proteins (soy); less than strict avoidance of the causal proteins; Low exposure to TLR ligands in the environment (dust endotoxin, pet ownership, number of siblings, daycare, antibiotic use, etc); and the severity of atopic dermatitis.