Pepstatin A-sensitive aspartic proteases in lysosome are involved in degradation of the invariant chain and antigen-processing in antigen presenting cells of mice infected with Leishmania major
Tq. Zhang et al., Pepstatin A-sensitive aspartic proteases in lysosome are involved in degradation of the invariant chain and antigen-processing in antigen presenting cells of mice infected with Leishmania major, BIOC BIOP R, 276(2), 2000, pp. 693-701
Citations number
38
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
We previously reported that CA074, a specific inhibitor of cathepsin B, sig
nificantly deviated immune responses hom the disease-promoting Th2 type to
the protective Th1 type in BALB/c mice infected with Leishmania major. Here
in, we found that pepstatin A-sensitive aspartic proteases (PSAP) in lysoso
mes seem to play a different role from that of cathepsin B in antigen-proce
ssing and Ii-degradation. That is, cathepsin B appears to digest 16-, 28-,
and 31-kDa peptides of soluble leishmania antigen (SLA), whereas PSAP seems
to process mainly 28-kDa peptides. Furthermore, the latter protease contri
buted to the degradation of Ii but cathepsin B did not. Following treatment
with pepstatin A, both Th1 and Th2 responses were profoundly suppressed in
resistant DBA/2 mice (H-2(d)) and in susceptible BALB/c mice (H-2d), and b
oth strains of mice became markedly susceptible compared with the untreated
groups, probably owing to failure in degradation of Ii and partly to failu
re in digestion of 28-kDa peptide. (C) 2000 Academic Press.