Thimet oligopeptidase (EC 3.4.24.15), a novel protein on the route of MHC class I antigen presentation

The initial processing of antigens leading to major histocompatibility comp lex (MHC) class I antigenic peptides is carried out by the proteasome, Howe ver, how the final epitopes are generated and protected from degradation by cytosolic peptidases remains unknown, Coincidentally, peptides associated with the MHC class I molecules range from 8 to 13 amino acid residues, simi larly to the optimum substrate size required for the cytosolic thimet oligo peptidase, Here we have investigated the putative intracellular function of thimet oligopeptidase related to antigen presentation. Using a well-charac terized antigen-presenting cell system, we were able to demonstrate either inhibition or stimulation of CD8 T cell proliferation and cytotoxicity, man ipulating intracellular thimet oligopeptidase levels with its specific inhi bitor cFP-Ala-Ala-Tyr-pAb or loading the enzyme itself into the antigen-pre senting cells. Our results suggest that thimet oligopeptidase should take a n important function in the pathway of antigen presentation via MHC class I through a mechanism yet unknown, (C) 1999 Academic Press.