P1-202 Development and Characterization of Novel R5-like Monoclonal Antibodies Directed against Gluten

Sunday, July 26, 2015
Exhibit Hall (Oregon Convention Center)
David Cox , IEH Laboratories & Consulting Group , Lake Forest Park , WA
Madhu Katepalli , IEH Laboratories & Consulting Group , Lake Forest Park , WA
Brianda Barrios-Lopez , IEH Laboratories & Consulting Group , Lake Forest Park , WA
Charles Kainrath , IEH Laboratories & Consulting Group , Lake Forest Park , WA
Mahzad Meshgi , IEH Laboratories & Consulting Group , Lake Forest Park , WA
Lora Benoit , IEH Laboratories & Consulting Group , Lake Forest Park , WA
Jeffrey Day , IEH Laboratories & Consulting Group , Lake Forest Park , WA
Cesar Nadala , IEH Laboratories and Consulting Group , Lake Forest Park , WA
Mansour Samadpour , IEH Laboratories & Consulting Group , Lake Forest Park , WA
Introduction: Cereal grains contain a composite protein called gluten which consists of prolamins and glutenins. The prolamin fraction from wheat and related triticeae cereals exhibits immunopathogenic potential, and consumption of these grains is associated with symptoms of celiac disease. The current gold standard for detection of gluten residues used in the food industry relies on the use of immunodiagnostic tests based on the R5 monoclonal.

Purpose: In an effort to obtain novel serological reagents with improved specificity profiles relative to the R5 system, we generated monoclonal antibodies in mice. Herein, we describe the immuno-reactive profile of the candidate clones and compare their binding activity against that of the R5 mAb.

Methods: A combination of deamidated gliadin and synthetic R5-peptide (LQPQQPFPQQLQPQQPFPQQA) was used to immunize female Balb/C mice. Spleens from seroconverted mice were fused with SP2/0-Ag14 cells and cultured using HAT techniques. Colonies were screened and initially selected based on reactivity towards gliadin, hordein, secalin, and avenin using indirect ELISA. IgG+ clones that retained high activity were raised and IgG purified from ascites was further studied by ELISA and western blot analysis and used to develop a sandwich ELISA.

Results: Using a combined vaccine approach, two hybridoma clones were generated, 2B9 and 1A11, which demonstrated very high, and near equal activity against gliadin, hordein, and secalin, and no cross-reactivity against avenin, zein, orzenin, or soy as determined by indirect ELISA. Western blot analysis of these two clones demonstrated a pattern of reactivity that mirrored that of the R5 mAb. Both clones were conjugated to HRP and used to develop sandwich ELISAs. 

Significance: Of the clones tested, 1A11 and 2B9 demonstrated the most potential for use in future gluten detection systems, including use in sandwich ELISA for detection of wheat, barley, and rye-derived gluten residues.