Unlike TG. The generation of gliadin-reactive T cells are

Unlike
other autoimmune diseases, in coeliac disease the trigger factor is uniquely identifiable
as gluten. The main causative agents of the disease are dominant HLA and
autoantibodies against Thyroglobulin which was detected in more than 95% of individuals
in coeliac disease4.

The
pathogenesis of coeliac disease is proposed to be by different pathways which
leads to destruction of epithelium and villous atrophy caused by gluten which
is the storage protein found in wheat, barley and rye. Gliadin is a
glycoprotein extract from gluten that causes the overexpression of IL-5 in the
intestine that is considered to be toxic to enterocyte. It also upregulates the
MIC-A stress molecule on the surface of enterocytes and NKG2D receptor on the
infiltrating intraepithelial lymphocytes thus promoting a lymphocyte-mediated
cytotoxic response towards the enterocytes which depends on IL-15.TG has a
pivotal role in the pathogenesis of coeliac disease, gliadin is ingested into
enzyme crosslinks causing specific deamidation of glutamine into glutamic acid
within the gliadin peptides. This deamidation process makes the gliadin
peptides more open to the gliadin -reactive CD-4 T cells in context of MHC-DQ2 molecule
thus increasing immunogenicity. Gliadin is believed to be less immunogenic and
might not stimulate T cells efficiently without TG. Gliadin is very rich
proline residues which is resistant to digestion in the intestine and binds
with DQ2 molecules. The absorption of these large intact peptides of gliadin is
believed to initiate immunogenic response 5.

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TG plays
an important role in the molecular level as in involved in deamidation of
gliadin and crosslinking, but there is very little evidence to support the
theory that TG has an immunologic role. The TG autoantibodies are believed to
form by antigen presenting cells targeting the toxic gliadin peptides taking up
TG-gliadin complexes resulting in immune reaction against gliadin and TG. The
generation of gliadin-reactive T cells are a combined effect of adaptive and
innate immune system, leading to a cytotoxic response and antibody formation5.hh