Scientists have finally homed in on a specific subset of immune cells that are central to allergies, clearing up the longstanding mystery behind why some individuals develop allergic diseases, and potentially identifying new therapeutic targets. Almost 50 million Americans suffer from nasal allergies, and life-threatening food allergies can cause as many as 200 deaths per year in the United States. Allergic reactions arise from an inappropriate immune response to otherwise innocuous substances such as pollen, mold, or peanuts, initiated by a group of immune cells known as the TH2 subset, or type 2 "helper" T cells. Until now, scientists have been unable to distinguish allergy-causing TH2 cells from the genuinely helpful cells that play vital roles in defending the body against pathogens. Now, Erik Wambre et al. identified a distinctive signature of six surface markers that sets problematic TH2 cells apart in allergies. The allergy-inducing cells (dubbed TH2A), were present in 80 individuals allergic to a variety of substances including tree pollen, mold, house dust-mites, and peanuts, but not in 34 people without allergies. TH2A cells produced multiple inflammatory signaling molecules, and the researchers further observed unique gene expression patterns in TH2A cells involving pathways that drive allergic responses. In a clinical trial evaluating the efficacy of an experimental peanut allergy treatment, the scientists noted a direct correlation between desensitization to nuts and decreased frequency of TH2A cells. According to the authors, the cells could be used as much-needed clinical biomarkers to evaluate the effectiveness of allergy treatments. A Focus by David J. Cousins further highlights the potential importance of these findings.