When Gluten-Free Isn’t Enough: The Corn-Wheat Overlap Epitope


An epitope is the part of an antigen that is recognized by the immune system. For example, the epitope is the specific piece of the antigen to which an antibody binds.

image from The Free Dictionary: “Epitope” https://medical-dictionary.thefreedictionary.com/epitope

Epitope mapping is the process of experimentally identifying the binding sites, or ‘epitopes’, of antibodies on their target antigens. Other than the identified antigens, corn has overlapping peptides (epitopes) with wheat.

Wheat and corn sensitivity

Because corn has been the most common alternative to wheat in gluten-free food, these overlapping epitopes can be problematic for wheat sensitive individuals who are on a gluten-free diet but not corn-free diet.


Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet.

However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as corn.

Corn may cause gluten-sensitive individuals to react just as strongly

Corn is one of the most common alternatives to wheat used in a gluten-free diet. In some CD patients, as a rare event, peptides from corn prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides [1].

cornwheat epitope quote

This is supported by several shared features between wheat and corn prolamins and by some experimental results.

Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from corn prolamins could also be tested to determine whether they also induce a cellular immune response.

Pepsin and trypsin, the main peptidases of the intestinal tract, cannot completely digest wheat gluten, because they are unable to cut its 15% proline-containing polypeptides.

The result is the release of peptides larger than nine amino acids, which are capable of eliciting innate and adaptive immune responses.

Corn has similar prolines as wheat

The proline content of zeins is also high (9%) and, although zeins contain bonds that pepsin can cut, they also contain cysteine residues with disulfide bonds that obstruct digestion by pepsin.

Altogether, the ability of trypsin to digest zeins is low due to their low number of cleavage sites, low solubility and secondary conformation.

Although the levels of antibodies against gluten decrease in some CD patients following gluten free diet, antibodies against corn prolamins remained high until both gluten and corn were removed from the diet.

At Vibrant, in addition to testing of gluten and non-gluten wheat peptides on the Wheat Zoomer, we offer testing for the Corn-Wheat overlap epitope, on the Corn Zoomer test.


1. Ortiz-Sanchez et al. (2013). “Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients.” Nutrients. 2013 Oct; 5(10): 4174–4183. http://europepmc.org/articles/pmc3820067

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