Allergic reactions to legumes range from mild skin rashes to life-threatening systemic anaphylaxis. These reactions are caused by naturally occurring proteins in the plant that upon interaction with the immune system of allergic patients, trigger the production allergen-specific IgE antibodies. Soybean is considered one of the eight most allergenic foods and, along with peanut, are the most important legumes associated with food allergies. Currently, the only method to manage soybean allergy is to remove it from the diet. However, this has proven virtually impossible for the majority of soy-allergic patients because soy products are "hidden" in many processed foods. Despite the fact that several soybean allergens have already been characterized, the goal of this investigation was to identify and characterize novel soy allergens, since these data might be used in the development of therapeutic agents to treat soy-allergic patients. Further, because recent investigations have demonstrated the potential use of soybean protein to desensitize people with more severe allergy to foods such as peanut, the identification of novel soy allergens could also advance the development of this desensitization strategy. Because plant food allergens belong to a small number of protein families present in a wide array of species, we hypothesized that soy proteins that are orthologs of proteins known to be allergenic in other crop species could also be allergens in soy. In this investigation we constructed a cDNA library from developing soy seeds and isolated four full-length cDNAs encoding novel candidate allergens. The proteins these cDNA encoded were expressed in a bacterial system and were analyzed by a combination of genomic, proteomic and immunological techniques. The results presented here demonstrate that we have characterized a novel soybean allergen, the seed specific biotinylated protein (SBP). Our results also indicate that SBP is potentially a major allergen because it exhibits reactivity with the majority of soy-allergic patient sera tested in the study. Further characterization of this protein has led us to hypothesize that the peanut ortholog of soy SBP is also allergenic. The soybean SBP is thus an important allergen and should be considered in the diagnosis and treatment of soybean allergy.