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.
Stig Tollefsen, Helene Arentz-Hansen, Burkhard Fleckenstein, Øyvind Molberg, Melinda Ráki, William W. Kwok, Günther Jung, Knut E.A. Lundin, Ludvig M. Sollid
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.