<jats:title>Abstract</jats:title> <jats:p>According to WHO estimates, more than 1.5 billion people (&amp;gt;24% worldwide) are living with some type of helminth infection and there is no FDA-approved anti-helminth vaccine available. The type 2 immune response is understood to be involved in our defense against helminth infection. In developing countries, elevated serum IgE level is a hallmark of parasitic disease. However, many aspects of the human immune response to helminth infection are still unknown; including, the identity of helminth proteins targeted by IgE antibodies and the size and complexity of the functional IgE repertoire. In this study, we have generated and characterized first ever panels of full-length naturally occurring human helminth specific IgE mAbs. We isolated IgE B cells from individuals with helminth infection and used human hybridoma technology to generate IgE mAbs. ELISA and Western blot techniques were used to test binding of purified IgE mAbs to helminth lysate. The helminth proteins targeted by IgE mAbs were determined using immunoprecipitation, mass spectrometry and de novo peptide sequencing techniques. The information obtained regarding IgE targets and their immune dominance will assist in our basic understanding of the role IgE plays in defending us against helminth infection and will ultimately aid in the rational design of anti-helminth vaccines. Lastly, we analyzed IgE mAb sequences and found remarkable variation in antibody variable region gene usage as well as mutation frequency.</jats:p>