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Immune‐mediated hypersensitivities such as autoimmunity, allergy, and allogeneic graft rejection are treated with therapeutics that suppress the immune system, and the lack of specificity is associated with significant side effects. The delivery of disease‐relevant antigens (Ags) by carrier systems such as poly(lactide‐co‐glycolide) nanoparticles (PLG‐Ag) and carbodiimide (ECDI)‐fixed splenocytes (SP‐Ag) has demonstrated Ag‐specific tolerance induction in model systems of these diseases. Despite therapeutic outcomes by both platforms, tolerance is conferred with different efficacy. This investigation evaluated Ag loading and total particle dose of PLG‐Ag on Ag presentation in a coculture system of dendritic cells (DCs) and Ag‐restricted T cells, with SP‐Ag employed as a control. CD25 expression was observed in nearly all T cells even at low concentrations of PLG‐Ag, indicating efficient presentation of Ag by …