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HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease
Stig Tollefsen, … , Knut E.A. Lundin, Ludvig M. Sollid
Stig Tollefsen, … , Knut E.A. Lundin, Ludvig M. Sollid
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2226-2236. https://doi.org/10.1172/JCI27620.
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Research Article Gastroenterology

HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease

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Abstract

Celiac disease is associated with HLA-DQ2 and, to a lesser extent, HLA-DQ8. Type 1 diabetes is associated with the same DQ molecules in the opposite order and with possible involvement of trans-encoded DQ heterodimers. T cells that are reactive with gluten peptides deamidated by transglutaminase 2 and invariably restricted by DQ2 or DQ8 can be isolated from celiac lesions. We used intestinal T cells from celiac patients to map DQ2 and DQ8 epitopes within 2 representative gluten proteins, α-gliadin AJ133612 and γ-gliadin M36999. For α-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of 2 separate regions. For γ-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of the same region. Some γ-gliadin peptides were recognized by T cells in the context of DQ2 or DQ8 when bound in exactly the same registers, but with different requirements for deamidation; deamidation at peptide position 4 (P4) was important for DQ2-restricted T cells, whereas deamidation at P1 and/or P9 was important for DQ8-restricted T cells. Peptides combining the DQ2 and DQ8 signatures could be presented by DQ2, DQ8, and trans-encoded DQ heterodimers. Our findings shed light on the basis for the HLA associations in celiac disease and type 1 diabetes.

Authors

Stig Tollefsen, Helene Arentz-Hansen, Burkhard Fleckenstein, Øyvind Molberg, Melinda Ráki, William W. Kwok, Günther Jung, Knut E.A. Lundin, Ludvig M. Sollid

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Figure 3

Testing for T cell recognition of variants of the228 SGQGSFQPSQQ NPQ241 peptide of AJ133612 α-gliadin.

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                  Testing for T cell recognition of variants of the228
...
The peptide harbors the DQ8–α-I epitope. A peptide with the native sequence and peptides with Q→E substitutions in P1 (position 230), P9 (position 238), and P1/P9 were tested for their ability to stimulate 2 DQ8-restricted T cell clones, TCC489.2.1.4 (A) and TCC360-HTLR8 (B), which were derived from 2 different DQ2–DQ8+ patients. Responses are shown as cpm × 103. TG2-treated, native sequence treated with TG2, used as a control.
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