aGlia = gliadin-derived; Hor = hordein-derived; Sec = secalin-derived; Av = avenin-derived.

aGlia = gliadin-derived; Hor = hordein-derived; Sec = secalin-derived; Av = avenin-derived.

HLA-DQ8 prefers negatively charged residues. Strikingly, tTG was found to selectively modify this peptide through conversion of the glutamine residues at the pi and p9 positions into glutamic acid (van de Wal et al., 1998b). As the result of this modification, a 100-fold less of the peptide was required for optimal T cell stimulation. Similarly, others identified an HLA-DQ2-restricted gliadin peptide and found that this peptide was only recognized after deamidation of particular Q residues, either as a result of chemical modification or treatment with tTG (Molberg et al., 1998; Sjostrom et al., 1998). In subsequent studies, a large number of gluten peptides have been identified that can stimulate T cells of CD patients (Arentz-Hansen et al., 2000, 2002; van de Wal et al., 2000; Vader et al., 2002a,b). It was also observed that some of those peptides cluster in regions that are resistant to degradation by enzymes in the gastrointestinal tract, resulting in highly immunogenic multivalent gluten fragments (Shan et al., 2002). Importantly, it also became clear that T cell responses to more than one gluten peptide are found in all patients. All of them give rise to the secretion of inflammatory cytokines, and are likely involved in the disease process (Vader et al., 2002a).

Most of the peptides identified to date require modification by tTG before they can bind to HLA-DQ2 and stimulate T cells. Thus, modification of gluten by tTG plays an important role in the generation of an extensive repertoire of T cell stimulatory gluten peptides. It should be noted, however, that several gluten pep-tides do not require tTG modification for T cell recognition (van de Wal., 2000; Vader et al., 2002a), indicating that native gluten can also induce T cell reactivity.

It should also be pointed out that gluten might also act through the innate arm of the immune system. Recent studies indicate that activation of the innate immune system by gliadin strongly enhances the gluten-specific T cell response (Maiuri et al., 2003). The actual mechanism through which gluten exerts this effect, however, remains to be determined.

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Why Gluten Free

Why Gluten Free

What Is The Gluten Free Diet And What You Need To Know Before You Try It. You may have heard the term gluten free, and you may even have a general idea as to what it means to eat a gluten free diet. Most people believe this type of diet is a curse for those who simply cannot tolerate the protein known as gluten, as they will never be able to eat any food that contains wheat, rye, barley, malts, or triticale.

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