Abstract Adoptive immunotherapy is a promising strategy in the battle against cancer and infectious diseases and the recently developed artificial antigen-presenting cell (aAPC) overcomes several obstacles for this therapy. The aAPC recapitulates the natural in vivo antigen-presenting cell (APC)–T cell interactions by coupling human leukocyte antigen–immunoglobulin fusion protein (HLA–Ig), a soluble multivalent HLA–Ig chimeric fusion protein, to beads. The natural ligand–receptor interaction promotes rapid sustained expansion and normal functioning of the antigen-specific T cells.