Katunuma N, Matsunaga Y, Saibara T
Institute for Health Sciences, Tokushima Bunri University, Japan.
Adv Enzyme Regul. 1994;34:145-58. doi: 10.1016/0065-2571(94)90014-0.
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.
组织蛋白酶B的特异性抑制剂、抗组织蛋白酶B抗体以及组织蛋白酶B的特异性底物，可抑制针对乙肝和狂犬病疫苗作为抗原的细胞免疫和体液免疫反应。这些疫苗的抗原肽由组织蛋白酶B加工处理，其片段能够与MHC II类β链的去表位结合，因为组织蛋白酶B的一个活性位点（14, 15）VN217 - 222与MHC II类β链去表位的一部分VN57 - 62具有高度同源性。对这些疫苗分子合成抗原肽的再次刺激显示，对由这些疫苗致敏的脾细胞有强烈的增殖反应。然而，组织蛋白酶B抑制剂并未抑制对这些抗原肽的反应。这些发现表明，组织蛋白酶B抑制剂除了抑制抗原的蛋白水解加工外，并不抑制免疫反应的任何其他过程。一些研究者最近报道，Ii链在体外可被纯化的组织蛋白酶B降解（23 - 25）。然而，我们发现组织蛋白酶B抑制剂对这些免疫反应的抑制并非由于抑制了恒定链的降解。我们发现恒定链与半胱氨酸蛋白酶的内源性抑制剂胱抑素家族具有约40%的同源性（23, 24）。因此，Ii链是胱抑素超家族的成员之一，可能参与抗原肽提呈的调节以及组织蛋白酶B对抗原的加工处理。
