Both cathepsin B and cathepsin D are necessary for processing of ovalbumin as well as for degradation of class II MHC invariant chain

• Published in: Immunology letters Vol. 43; no. 3; pp. 189 - 192
• Main Authors: Mizuochi, Toshiaki, Yee, Sung-Tae, Kasai, Michiyuki, Kakiuchi, Terutaka, Muno, Daisaku, Kominami, Eiki
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.1994
• Subjects: Animals; Antigen Presentation - immunology; Antigen processing/presentation; Antigen-Presenting Cells - immunology; Antigens, Differentiation, B-Lymphocyte; B-Lymphocytes - immunology; Cathepsin; Cathepsin B - antagonists & inhibitors; Cathepsin B - immunology; Cathepsin D - antagonists & inhibitors; Cathepsin D - immunology; Cell Line; Class II MHC; Cysteine Proteinase Inhibitors - pharmacology; Dipeptides - pharmacology; Histocompatibility Antigens Class II - immunology; Humans; Interleukin-2 - biosynthesis; Invariant chain; Leucine - analogs & derivatives; Leucine - pharmacology; Major Histocompatibility Complex - immunology; Mice; Ovalbumin - immunology; Pepstatins - pharmacology; T-Lymphocytes, Helper-Inducer - immunology; Tumor Cells, Cultured; Class II MHC; Ii; Cathepsin; APC; Th; Antigen processing/presentation; MHC; Invariant chain; OVA
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/0165-2478(94)90221-6

The effect of highly selective inhibitors of cathepsins on the processing of ovalbumin (OVA) and the presentation of an OVA-derived antigenic peptide (OVA 323–339) by antigen presenting cells (APC) was investigated. Both CA-074 (a specific inhibitor of cathepsin B) and pepstatin A (a specific inhibitor of cathepsin D) showed an inhibitory effect on the IL-2 production from an OVA-specific, I-A d-restricted helper T (Th) cell clone upon stimulation with OVA presented by the I-A d-positive APC. In contrast, the presentation of the antigenic epitope, OVA 323–339, to the same Th clone was not inhibited by either CA-074 or pepstatin A alone, nor even by the mixture of both inhibitors. When APC were treated with cathepsin inhibitor for 24 h, and then antigen and Th were added to the culture, the presentation of not only OVA but also an OVA-derived antigenic peptide was inhibited by either cathepsin inhibitor alone. In addition, the expression of invariant chain on APC was significantly augmented by the pretreatment of APC with either cathepsin inhibitor. Two main conclusions are drawn from these results. First, not only aspartyl protease, such as cathepsin D, but also thiol protease, such as cathepsin B, is involved in antigen processing by APC. Second, both cathepsin B and cathepsin D are necessary for degradation of the invariant chain (Ii) from the MHC class II αβ heterodimer in endosomes in order to express functional MHC class II molecules for binding antigenic peptides.