Proteasomes are the proteolytic complex responsible for major histocom
patibility complex (MHC) class I-restricted antigen presentation. Inte
rferon gamma treatment increases expression of MHC-encoded LMP2 and LM
P7 subunits of the proteasome and decreases expression of two proteaso
me subunits, named X and Y, which alters the proteolytic specificity o
f proteasomes. Molecular cloning of complementary DNAs encoding X and
Y showed that their proteins are proteasomal subunits with high amino
acid similarity to LMP7 and LMP2, respectively. Thus, interferon gamma
may induce subunit replacements of X and Y by LMP7 and LMP2, respecti
vely, producing proteasomes perhaps more appropriate for the immunolog
ical processing of endogenous antigens.