Rp. Anderson et al., In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope, NAT MED, 6(3), 2000, pp. 337-342
Citations number
22
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Celiac disease (CD) is an increasingly diagnosed enteropathy (prevalence, 1
:200-1:300)(1) that is induced by dietary exposure to wheat gliadins(2) (as
well as related proteins in rye and barley) and is strongly associated wit
h HLA-DQ2 (alpha 1*0501, beta 1*0201), which is present in over 90% of CD p
atients(3). Because a variety of gliadin peptides have been identified as e
pitopes for gliadin-specific T-cell clones(4-6) and as bioactive sequences
in feeding studies and in ex vivo CD intestinal biopsy challenge(7-9), it h
as been unclear whether a 'dominant' T-cell epitope is associated with CD.
Here, we used fresh peripheral blood lymphocytes from individual subjects u
ndergoing shortterm antigen challenge and tissue transglutaminase-treated,
overlapping synthetic peptides spanning A-gliadin to demonstrate a transien
t, disease-specific, DQ2-restricted, CD4 T-cell response to a single domina
nt epitope. Optimal gamma interferon release in an ELISPOT assay was elicit
ed by a 17-amino-acid peptide corresponding to the partially deamidated pep
tide of A-gliadin amino acids 57-73 (Q65E). Consistent with earlier reports
indicating that host tissue transglutaminase modification of gliadin enhan
ces gliadin-specific CD T-cell responses(10), tissue transglutaminase speci
fically deamidated Q65 in the peptide of A-gliadin amino acids 56-75. Disco
very of this dominant epitope may allow development of antigen-specific imm
unotherapy for CD.