Specific monoclonal antibodies block the presentation of InsB peptides by WBCs and reduce diabetes penetrance. (A) Responses of the InsB:13-21– and InsB:12-20–specific CD4 T cells to blood leukocytes obtained from NOD mice with or without injection of a mixture of anti–InsB:9-23 and anti–InsB:1-30 antibodies before glucose challenge. The anti–I-A^g7 antibody was added to the T cell–leukocyte culture as a control. Data (mean ± SEM) summarize results pooled from three independent experiments; each point represents one biological replicate including two to six mice. ****, P < 0.001; Mann–Whitney test. (B) Diabetes incidence of female NOD mice administered with the mixture of anti–InsB:9-23 and anti–InsB:1-30 antibodies. The control mice were given polyclonal mouse IgG. Data summarize the percent of diabetes (21 mice per group) from three independent experiments. **, P < 0.005; log-rank test. (C and D) Cohorts of female NOD mice were given the anti-InsB antibody mixture or control mouse IgG weekly at 4, 5, and 6 wk of age, and the islets were analyzed for leukocyte infiltration by flow cytometry at 9 wk of age. (C) Representative FACS plots showing the gating strategy of the immune cell components in the islets, including the CD45⁺ leukocytes, CD4 and CD8 T cells, DCs, and the resident macrophages (Mac). (D) Percentage of the indicated immune cell populations, as depicted in C, among the total islet cells. Data represent results obtained from individual mice (each point) examined in three independent experiments. *, P < 0.01; **, P < 0.005; Mann–Whitney test. CPM, counts per minute; SSA, side scatter A.