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

S Tollefsen, H Arentz-Hansen… - The Journal of …, 2006 - Am Soc Clin Investig
S Tollefsen, H Arentz-Hansen, B Fleckenstein, Ř Molberg, M Ráki, WW Kwok, G Jung…
The Journal of clinical investigation, 2006Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation