Extended Data Fig. 6: HLA-DQ8 is required for the expansion of cytotoxic IELs.

a, Cells were isolated from the mesenteric lymph nodes of DQ8-D^d-villin-IL-15tg and D^d-villin-IL-15tg mice. CD11c⁺CD103⁺ dendritic cells were analysed by flow cytometry for their expression of MHC class II and HLA-DQ8 molecules. b–f, DQ8-D^d-villin-IL-15tg and D^d-villin-IL-15tg mice raised on a GFD were maintained on a GFD or fed gluten for 30 days. b, Serum levels of anti-DGP IgG antibodies were measured by ELISA. Serum was collected 30 days after gluten feeding (DQ8-D^d-villin-IL-15tg, sham n = 17, gluten n = 28; D^d-villin-IL-15tg, sham n = 17, gluten n = 28). c, Expression of Ifng in the lamina propria was measured by qPCR. Relative expression levels in gluten groups were normalized against the expression levels observed in sham-fed DQ8-D^d-villin-IL-15tg mice and sham-fed D^d-villin-IL-15tg (DQ8-D^d-villin-IL-15tg, n = 8; D^d-villin-IL-15tg, n = 9). d–f, The intestinal epithelium was isolated and analysed by flow cytometry. IELs were identified as TCRβ⁺CD4⁻CD8⁺ cells. d, NKG2D⁺NKG2⁻ IELs are indicated by absolute number per 100 IECs (DQ8-D^d-villin-IL-15tg, sham n = 8, gluten n = 16; D^d-villin-IL-15tg, sham n = 9, gluten n = 22). e, Granzyme B⁺ IELs are indicated by absolute number per 100 IECs (DQ8-D^d-villin-IL-15tg, sham n = 8, gluten n = 8; D^d-villin-IL-15tg, sham n = 9, gluten n = 10). f, MFI of intracellular granzyme B (DQ8-D^d-villin-IL-15tg, sham n = 5, gluten n = 6; D^d-villin-IL-15tg, sham n = 5, gluten n = 5). Data are mean values (b, d–f) or mean ± s.e.m. (c) from six (b, d), three (c), four (e) or two (f) independent experiments. P values were determined by ANOVA with Tukey’s multiple comparison test (b, d–f) or unpaired, two-tailed, t-test (c).

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