Cellular and humoral immune responses to vaccines of hepatitis B type and rabies were inhibited by specific inhibitors of cathepsin B, specific synthetic substrates of cathepsin B and anti‐cathepsin B antibody. Therefore the lysosomal cathepsin B of antigen presenting cells plays an essential role in processing of these antigens for presentation to MHC class II. One of the active sites of cathepsin B, VN_217–222 shares highly homologous sequences with a part of the desetope, a binding domain of antigenic peptides, VN_57–62 of MHC class II, β‐chain. This evidence suggests that the peptides processed by the substrate specificity of cathepsin B exhibit a common affinity to bind with the desetope of MHC class II, β‐chain.