Allergen Structure and Function

Asthma and other allergic diseases affect up to 30% of some populations in developed countries. The direct medical costs and societal costs (e.g., missed days in school and lost productivity at work) have a major impact on our personal productivity and health care system, which impacts the U.S. economy as a whole. The goal of this long-term collaborative, multidisciplinary research program is to understand the allergic process in enough detail to be able to prevent the development or effectively ameliorate allergic responses that lead to asthma and other allergic diseases. We are particularly interested in the specific reactions to the allergens from various regional plants.

Our structural allergy research group is applying two major approaches to better understand how an otherwise harmless plant protein “fools” our immune system into making vigorous and detrimental allergic responses. Our first approach consisted of detailed studies of the structure of allergens to define what distinguishes them from other proteins, to which we are similarly exposed. The allergenic proteins that cause mountain cedar allergy in our region (“cedar fever”) are providing an excellent model system for this approach. The second approach has been to develop an online, comprehensive, structural database of allergenic proteins (SDAP) that brings together a listing of all of the known allergens (approximately 800) and links these to various sources of structural information. Together these two approaches are providing new computational tools for recognizing which proteins have the potential to induce allergic responses from the human immune system.

Our current ongoing approach is to identify the structures of those regions of allergens that are recognized by the allergy-causing (mostly IgE) antibodies. For instance, we have produced a large set of monoclonal antibodies to the major allergen of mountain cedar pollen, Jun a 1, and identified what type of structures these antibodies bind. Our current understanding, derived from Jun a 1, and similar allergens from Southern Europe and Japan, is that the troublesome allergen binds to parts of these allergens that represent “knots” on the surface of the molecules, rather than just strings of amino acids. Interestingly we can make these “knots” relax into strings using chemical treatment, which also prevent the IgE antibodies from binding to the allergen, an important interaction in the development of allergic reactions. We have also found a unique antibody to Jun a 1 which, upon binging to Jun a 1, seems to loosen those critical knots, and thereby prevent allergic reactions, at least at the cellular level. We have produced a molecular mimic of this antibody, which can inhibit the first stage of allergic reactions by altering the interaction of IgE antibodies to those knotty regions on Jun a 1 and similar allergens.  



  • Database approach for prediction of food allergenicity. FDA CFSAN-02-1 (Braun). Goldblum role: Co-inv in charge of lab-based models. Total costs $741,720, 09/02-09/06.
  • Phylogenetic approach to plant allergy vaccines. NIH/NIAID R01 AI52428 (Goldblum), Total costs $1,057,000. 03/04-04/08.
  • Structural biology of cedar pollen allergy. NIH/NIAID K08 AI55792 (Midoro). Total costs $475,200, 04/04-03/08.
  • Cellular Response Mechanisms to Environmental Challenge. NIH/NIEHS P30 ES006676 (Elferink), Goldblum role: Associate Director for Translational Research & Director Asthma Pathogenesis Research Core. 10% effort. Total costs $7,977,276. 04/95-03/10. 
  • Prediction and Classification of Allergenicity in a Protein Family. NIH./NIAID R21 AI109090 (Braun). Goldblum role: Co-inv Total costs, $426,260, 08/14-07/17.

    Relevant Publications

    • Ivanciuc, O., V. Mathura, T. Midoro-Horiuti, W. Braun, R.M. Goldblum, and C. Schein. Detecting potential IgE-reactive sites on food proteins using a sequence and structures database, SDAP-food. J Agric and Food Chem. 51:3840-4837, 2003.
    • Midoro-Horiuti, T., V. Mathra, C.H. Schein, W. Braun, C.C.Q. Chin, S. Yu, M. Watanabe, J.C. Lee, E.G. Brooks, and R.M. Goldblum. Major linear IgE epitopes of mountain cedar pollen allergen Jun a 1 map to the pectate lyase catalytic site. Mol. Immunol. 40(8):555-62, 2003.
    • Boldogh, I., A. Bacsi, B. Choudhury, R. Alam, T. Hazra, S. Mitra, R. Goldblum, and S. Sur. ROS Generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J Clin Invest. 115: 2169-2179, 2005.
    • Czerwinski, EW, T. Midoro-Horiuti, M.A. White, E.G. Brooks, R.M. Goldblum. Crystal Structure of Jun a 1, the Major Cedar Pollen Allergen from Juniperus ashei reveals a Parallel ß-Helical Core. J Biol Chem. 280 (5):3740-6. 2005.
    • Midoro-Horiuti, T., C.H. Schein, V. Mathura, W. Braun, EW. Czerwinski, A. Togawa, Y. Kondo, T. Oka, M. Watanabe, R.M. Goldblum. Structural basis for epitope sharing between group 1 allergens of cedar pollen. Mol Immunol. 43:509-518, 2006.
    • Togawa, A., R.C. Panzani, M. Garza, R.M. Goldblum, T. Midoro-Horiuti. Identification of a major allergen of Italian cypress pollen based on homology and cross-reactivity. Ann. Allergy Asthma and Immunology. 97:336-42,2006. 
    • Varshney, S., R.M. Goldblum, M. Auton, C. Kearney, M. Watanabe and T. Midoro-Horiuti. Major mountain cedar allergen, Jun a 1 contains conformational as well as linear IgE epitopes. Mol. Immunol. 44:2782-5, 2007.
    • Goldblum, R.M., Ning, B., Judy, B.M., Holthauzen, L.M., van Bavel, J., Kamijo, A., and Midoro-Horiuti, T. A single mouse monoclonal antibody, E58 modulates multiple IgE epitopes on group 1 cedar pollen allergens. Mol Immunol. 74:106-12, 2016.