Splenic cathepsin L is maturated from the proform by interferon-gamma after immunization with exogenous antigens.
The processing of foreign protein antigens into peptides requires the participation of various endo/lysosomal proteases in antigen-presenting cells (APCs). In this study, a proenzyme of cathepsin L, procathepsin L, was found to be present in the spleens of naive mice, as demonstrated by immunoblotting. Interestingly, the maturation of cathepsin L from procathepsin L was strongly induced when the host BALB/c mice were immunized with ovalbumin or soluble leishmanial antigen, despite the fact that mouse albumin, a kind of self-antigen, did not have such a potential. Furthermore, foreign antigens, but not self-antigens, could increase the activity of cathepsin L, probably being mediated by interferon-gamma, as demonstrated by in vivo and in vitro experiments. As cathepsin L matured, the efficiency of antigen processing was increased in APCs. These results suggest that endo/lysosomal cathepsin L plays an important role in the immune regulation via antigen processing even in peripheral lymphoid tissues as well as in the thymus.
Zhang
T
T
Department of Parasitology and Immunology, University of Tokushima, School of Medicine, Kuramoto-cho 3, Tokushima, 770-8503, Japan.
Maekawa
Y
Y
Sakai
T
T
Nakano
Y
Y
Ishii
K
K
Hisaeda
H
H
Kominami
E
E
Katunuma
N
N
Asao
T
T
Himeno
K
K
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000008:administration & dosage; D001483:Base Sequence; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D017931:DNA Primers / Q000235:genetics; D010450:Endopeptidases; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D013154:Spleen / Q000201:enzymology* / Q000276:immunology*
D000941:Antigens; D017931:DNA Primers; D004792:Enzyme Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D010047:Ovalbumin; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C063905:procathepsin L; D056668:Cathepsin L; C534278:Ctsl protein, mouse