The endo/lysosomal protease cathepsin B is able to process conalbumin fragments for presentation to T cells.
The protein antigens conalbumin (CA) and ovalbumin (OVA) are known to require uptake into antigen-presenting cells (APC) for their presentation to major histocompatibility complex (MHC) class II-restricted T cells. In both cases proteolytic cleavage is thought to be a necessary step for the generation of the respective antigenic peptides. A specific inhibitor of the endosomal protease cathepsin B, Cbz-Phe-Ala-CHN2, blocks the presentation of both CA and OVA, whereas this inhibitor has no effect on the presentation of a processing-independent OVA peptide. Furthermore, the presentation of insulin, an antigen that needs processing but no proteolytic cleavage, is enhanced when cathepsin B is inhibited during antigen pulsing. When the APC were treated with an inhibitor of acid proteases, the CA response was not affected, while the presentation of OVA was diminished under these conditions. To estimate the relevance of these findings for the generation of the antigenic CA peptide, extracellular digestions of CA by cathepsin B were carried out. The fragment(s) present in these digests was recognized by T cells without further processing. Furthermore, the time-course of intra- and extracellular CA processing with respect to the capacity to stimulate T cells was similar. Taken together these data suggest that degradation by cathepsin B may be sufficient in vivo to generate the antigenic CA fragment. On the other hand, the blocking of cathepsin B does not appear to have an adverse effect on the general mechanisms of antigen presentation.
Gradehandt
G
G
Institut für Immunologie der Johannes Gutenberg Universität Mainz, Germany.
Ruede
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E
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000502:physiology*; D002402:Cathepsin D / Q000037:antagonists & inhibitors; D003207:Conalbumin / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D010446:Peptide Fragments; D003207:Conalbumin; D002401:Cathepsin B; D002402:Cathepsin D