The present invention concerns artificial antigen presenting cells (aAPCs) and methods of making and using the same, for example, to isolate, identify, and expand T cell populations specifically reactive against a disease-associated antigenic peptide, as well as to modulate responses of antigen-specific T cells both in vivo, ex vivo, and in vitro. Accordingly, the aAPCs of the invention can be used to treat conditions that would benefit from modulation of a T cell response, for example, autoimmune disorders, allergies, cancers, viral infections, and graft rejection. In certain preferred embodiments, the aAPCs are liposomes comprised of MHC:peptide complexes and accessory molecules. Other molecules, such as co-stimulatory molecules and adhesion molecules, can also be included in the compositions of the invention. In other embodiments, the aAPCs are comprised of a scaffold to which a plurality of MHC:peptide complexes and accessory molecules (as well as other molecules) can be attached at high density.