Fine specificity of monoclonal antibodies against celiac disease-inducing peptides in the gluteome

BACKGROUND: In celiac disease patients, peptides derived from dietary gluten are recognized by HLA-DQ2-restricted CD4⁺ T cells, which results in inflammation. Such immune-stimulatory peptides are found in both gliadins and glutenins. Monoclonal antibodies (mAbs) against these peptides can be used to screen food for the presence of such peptides. OBJECTIVE: We aimed to determine the specificity of 5 mAbs raised against T cell stimulatory peptides found in α- and γ-gliadins and in low- and high-molecular-weight glutenins and to compare it with the specificity of patient-derived T cells. DESIGN: The reactivity of the mAbs with gluten peptides, enzymatic gluten digests, and intact gluten proteins was determined and compared with that of gluten-specific T cells by using a combination of immunologic and biochemical techniques. Furthermore, the reactivity of the mAbs with gluten homologues in barley, rye, and oat was determined. RESULTS: The specificity of the mAbs largely overlaps with that of gluten-specific T cells. Moreover, mAbs detect several homologous peptides present in gluten proteins. All except the LMW-specific mAbs also detect storage proteins present in barley and rye, whereas the γ-gliadin-specific mAbs also recognize oat proteins. CONCLUSION: The mAbs raised against T cell stimulatory peptides in gliadins and glutenins allow a comprehensive screen for the presence of harmful gluten and gluten-like proteins and peptides in food products. They can thus be used to guarantee the safety of food for celiac disease patients.