Mechanism and regulation of antigen processing by cathepsin B.
Cellular and humoral immune responses to vaccines of hepatitis B and rabies as antigens were suppressed by specific inhibitors of cathepsin B, anti-cathepsin B antibody and the specific substrate of cathepsin B. The antigenic peptides of these vaccines are processed by cathepsin B and the fragments are capable of binding with the desetope of MHC class II, beta-chain, because one of the active sites of cathepsin B (14, 15) VN217-222 shares high homology with a part of the desetope, VN57-62, of MHC class II, beta-chain. Rechallenge of the synthesized antigenic peptides of these vaccine molecules shows a strong proliferative response to the splenocyte primed by these vaccines. However, the response to these antigenic peptides was not inhibited by cathepsin B inhibitors. These findings suggest that cathepsin B inhibitors do not inhibit any other processes of immune responses than the proteolytic processing of antigens. Some investigators reported recently that the Ii-chain is degraded by purified cathepsin B in vitro (23-25). However, we showed that the suppression of these immune responses by cathepsin B inhibitors is not due to the inhibition of invariant chain degradation. We found that the invariant chain shares about 40% homology with the cystatin family which are the endogenous inhibitors of cysteine proteases (23, 24). Therefore, the Ii-chain is one of the members of the cystatin superfamily and may participate in the regulation of presentation of antigenic peptides and also antigen processing by cathepsin B.
Katunuma
N
N
Institute for Health Sciences, Tokushima Bunri University, Japan.
Matsunaga
Y
Y
Saibara
T
T
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D020789:Cathepsin C; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015809:HLA-DR7 Antigen / Q000235:genetics; D017325:Hepatitis B Vaccines / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding; D011819:Rabies Vaccines / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology* / Q000378:metabolism
D015809:HLA-DR7 Antigen; D017325:Hepatitis B Vaccines; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011819:Rabies Vaccines; D014765:Viral Vaccines; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D020789:Cathepsin C