Fig. 1

a Illustration of murine GPR40 and its seven transmembrane domains (swissprot. acc. no: Q76JU9). In addition, the localization of the newly identified K^b/GPR40_187-195 and D^d/GPR40_236–244 epitopes in TMHs is shown. b RIP-B7.1 mice were injected with pCI (triangles; n = 5) or pCI/GPR40 DNA (circles; n = 5), and blood glucose levels and diabetes incidence (%) were determined over time. c Four GPR40-immune and diabetic RIP-B7.1 mice were injected twice with anti-CD8 antibodies (open circles; n = 2) and anti-CD4 antibodies (closed circles; n = 2), and blood glucose levels were measured in individual mice for 5 days. d Pancreatic sections from representative healthy and diabetic RIP-B7.1 mice were stained for insulin (middle panels) and CD8 T cells (left panels). e RIP-B7.1 mice (n = 3–4 per group) were injected with pCI/GPR40_1–87, pCI/GPR40_74–162, pCI/GPR40_150–237 and pCI/GPR40_226–300 vectors, and diabetes incidence was determined over time. f GPR40_187–195-specific tetramer⁺ CD8 T cells in the pancreata of healthy, pCI-immune (n = 3) and pCI/GPR40_150–237-immune diabetic (n = 5) RIP-B7.1 mice were analyzed by FCM. The mean percentage of GPR40_187–195-specific tetramer⁺ CD8 T cells ± SD is shown. In addition, representative dot blots for each group are shown. g PD-L1^−/− mice were injected with pCI/GPR40 (n = 5; upper panel) or coinjected with pCI/GPR40 and pCI/ppins (n = 5; lower panel) and diabetes incidence was determined over time. h, i PD-L1^−/− mice (n = 4–5) were injected with pCI (group 1) or pCI/GPR40 (group 2) or coinjected with pCI/GPR40 and pCI/ppins into the left and right tibialis anterior muscle (group 3). h Healthy mice were analyzed day 12 post immunization for IFN-γ⁺ GPR40_187–195-specific CD8 T cells in the spleen and tetramer⁺ CD8 T cells in the pancreas by FCM. i At the time of diabetes onset in group 3 (i.e., 4 weeks post immunization), IFN-γ⁺ ppins/(K^b/A_12–21)-, and IFN-γ⁺ K^b/GPR40_187–195-specific CD8 T cells in the spleen and tetramer⁺ K^b/GPR40-specific CD8 T cells in the pancreata were determined by FCM. h, i The mean percentages of IFN-γ⁺ and tetramer⁺ CD8 T cells ± SD are shown. Statistical differences between groups 1 and 2 and between groups 1 and 3 were determined by unpaired Student’s t test, and p values < 0.05 (*) and < 0.01 (**) were considered significant. ns, not significant