Step 2: T-cell activation and costimulation. Donor T cells that express positive or inhibitory costimulatory pathway receptors encounter host antigen-presenting cells (APCs) that express major histocompatibility complex (MHC) antigens and ligands for these receptors. A host peptide is shown in the context of MHC/T-cell receptor (TCR) interactions. The red boxes below the mouse and the human recipient serve to highlight distinct features between these species. MiH indicates minor histocompatibility; MiHa, minor histocompatibility antigen; and Ab, antibody.