Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis
E Tolosa, W Li, Y Yasuda, W Wienhold… - The Journal of …, 2003 - Am Soc Clin Investig
E Tolosa, W Li, Y Yasuda, W Wienhold, LK Denzin, A Lautwein, C Driessen, P Schnorrer…
The Journal of clinical investigation, 2003•Am Soc Clin InvestigStepwise degradation of the invariant chain (Ii) is required for the binding of antigenic
peptides to MHC class II molecules. Cathepsin (Cat) L in the murine thymus and Cat S in
peripheral APCs have both been implicated in the last step of Ii degradation that gives rise to
the class II–associated invariant chain peptides (CLIP). Cat V has been recently described
as highly homologous to Cat L and exclusively expressed in human thymus and testis, but
with no mouse orthologue. We report that Cat V is the dominant cysteine protease in cortical …
peptides to MHC class II molecules. Cathepsin (Cat) L in the murine thymus and Cat S in
peripheral APCs have both been implicated in the last step of Ii degradation that gives rise to
the class II–associated invariant chain peptides (CLIP). Cat V has been recently described
as highly homologous to Cat L and exclusively expressed in human thymus and testis, but
with no mouse orthologue. We report that Cat V is the dominant cysteine protease in cortical …
Stepwise degradation of the invariant chain (Ii) is required for the binding of antigenic peptides to MHC class II molecules. Cathepsin (Cat) L in the murine thymus and Cat S in peripheral APCs have both been implicated in the last step of Ii degradation that gives rise to the class II–associated invariant chain peptides (CLIP). Cat V has been recently described as highly homologous to Cat L and exclusively expressed in human thymus and testis, but with no mouse orthologue. We report that Cat V is the dominant cysteine protease in cortical human thymic epithelial cells, while Cat L and Cat S seem to be restricted to dendritic and macrophage-like cells. Active Cat V in thymic lysosomal preparations was demonstrated by active-site labeling. Recombinant Cat V was capable of converting Ii into CLIP efficiently, suggesting that Cat V is the protease that controls the generation of αβ-CLIP complexes in the human thymus, in analogy to Cat L in mouse. Comparison of Cat V expression between thymi from patients with myasthenia gravis and healthy controls revealed a significantly higher expression level in the pathological samples, suggesting a potential involvement of this protease in the immunopathogenesis of myasthenia gravis, an autoimmune disease almost invariably associated with thymic pathology.
The Journal of Clinical Investigation