The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides.
OBJECTIVE
Gluten (GLU)-specific T-cell responses in HLA-DQ2 positive adult celiac disease (CD) patients are directed to an immunodominant alpha-gliadin (GLIA) peptide that requires deamidation for T-cell recognition. The aim of the current study was to determine which GLU peptide(s) are involved early in disease.


METHODS
We have characterized the GLU-specific T-cell response in HLA-DQ2 positive children with recent onset CD.


RESULTS
We found that 50% of these patients do not respond to the alpha-GLIA peptide but to a diverse set of GLIA and glutenin (GLT) peptides, including 6 novel epitopes. Moreover, individual patients respond to distinct (combinations of) GLU peptides. T-cell cross-reactivity toward homologous GLIA and GLT peptides was observed, which might play a role in the initial spreading of the GLU-specific T-cell response. Although all pediatric patients displayed deamidation-dependent responses, deamidation-independent responses were found in the majority of patients as well. Finally, T-cell responses to 3 of these novel GLU peptides were found in adult CD patients.


CONCLUSIONS
The diversity of the GLU-specific T-cell response is far greater than was previously appreciated. Both adult and young CD patients can respond to a diverse repertoire of GLU peptides. The observation that T-cell responses to 3 of the novel peptides are independent of deamidation indicates that T-cell responses can be initiated toward native GLU peptides. The possibility that deamidation drives the GLU response toward immunodominant T-cell stimulatory peptides after disease initiation is discussed.
Vader
Willemijn
W
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
Kooy
Yvonne
Y
Van Veelen
Peter
P
De Ru
Arnoud
A
Harris
Diana
D
Benckhuijsen
Willemien
W
Peña
Salvador
S
Mearin
Luisa
L
Drijfhout
Jan Wouter
JW
Koning
Frits
F
D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000276:immunology*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D000939:Epitopes; D005903:Gliadin / Q000276:immunology*; D005983:Glutens / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000032:analysis; D006801:Humans; D007223:Infant; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D010446:Peptide Fragments; D005983:Glutens; D005903:Gliadin; C037302:glutenin