| Abstract: |
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. |
| Keywords: |
immunohistochemistry; adolescent; child; preschool child; protein expression; child, preschool; unclassified drug; human cell; dose response; mouse; animal; metabolism; animals; mice; complex formation; reverse transcription polymerase chain reaction; protein; dose-response relationship, drug; peptide; physiology; blotting, western; chemistry; tissue distribution; thymus; thymus gland; infant; infant, newborn; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; lasers; hla antigen class 2; recombinant proteins; recombinant protein; western blotting; newborn; peptides; epithelium cell; cathepsin; cathepsins; antigen binding; histocompatibility antigens class ii; myasthenia gravis; immunopathogenesis; enzyme active site; laser; cathepsin l; cathepsin s; cathepsin v; cysteine proteinase; cysteine endopeptidases; b lymphocyte antigen; invariant chain; antigens, differentiation, b-lymphocyte; class ii associated invariant chain peptide; humans; human; priority journal; article
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