CATHEPSIN-L - CRITICAL ROLE IN II DEGRADATION AND CD4 T-CELL SELECTION IN THE THYMUS

Degradation of invariant chain (li) is a critical step in major histoc ompatibility complex class II-restricted antigen presentation. Catheps in L was found to be necessary for li degradation in cortical thymic e pithelial cells (cTECs), but not in bone marrow (BM)derived antigen-pr esenting cells (APCs). Consequently, positive selection of CD4(+) T ce lls, was reduced. Because different cysteine proteinases are responsib le for specific li degradation steps in cTECs and BM-derived APCs, the proteolytic environment in cells mediating positive and negative sele ction may be distinct. The identification of a protease involved in cl ass II presentation in a tissue-specific manner suggests a potential m eans of manipulating CD4(+) T cell responsiveness in vivo.