(A) Transgenic mice develop hypertension in response to angiotensin II (Ang II) (n = 4). **P < 0.01, ***P < 0.001 by Student’s t test. (B) Transgenic mice expressing soluble forms of H-2D^b or H-2K^b were treated with Ang II to induce hypertension before splenocyte harvesting and culture. Shed MHC-I was adsorbed onto Ni-agarose beads, cocultured with T cells from WT mice, and T cell proliferation measured with serial dye dilution and flow cytometry. (C) CD8⁺ T cells proliferate if exposed to bead-bound H-2D^b, but not H-2K^b (n = 4). ***P < 0.001 by Student’s t test. (D) CD8⁺ T cell proliferation is only observed if both soluble H-2D^b and T cells are isolated from Ang II–treated animals, and treating transgenic mice with the IsoLG scavenger 2-HOBA or blocking T cell–MHC-I interactions with the anti-IsoLG antibody D11 inhibits CD8⁺ T cell activation (n = 4–11). APCs, antigen-presenting cells. **P < 0.01 vs. No Treatment Ang II APCs + Ang II T cells by 2-way ANOVA and Holm-Šidák post hoc test. (E) After treating mouse DCs with tBHP to induce IsoLG adduct formation, cells were stained with antibodies for MHC-I and IsoLG conjugated to a complementary FRET fluorophore pair. FRET signal was observed when staining for H-2D^b and IsoLG in tBHP-treated DCs, but not untreated cells or when staining for H-2K^b (n = 3). All data are presented as mean ± SD. ***P < 0.001 by Student’s t test.