The invention disclosed herein is directed to methods of identifying a
polypeptide suitable for epitope liberation including, for example, the
steps of identifying an epitope of interest; providing a substrate
polypeptide sequence including the epitope, wherein the substrate
polypeptide permits processing by a proteasome; contacting the substrate
polypeptide with a composition including the proteasome, under conditions
that support processing of the substrate polypeptide by the proteasome;
and assaying for liberation of the epitope. The invention further relates
to vectors including a housekeeping epitope expression cassette and also
vectors including epitope cluster regions. The housekeeping epitope(s)
can be derived from a target-associated antigen. The housekeeping epitope
can be liberatable, that is capable of liberation, from a translation
product of the cassette by immunoproteasome processing. The invention
also relates to a method of activating a T cell comprising contacting a
substrate polypeptide with an APC and contacting the APC with a T cell.