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Original Article

^a Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
^b Institute of Biochemistry, Charité, Humboldt University, 10117 Berlin, Germany
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.31-71-521-675131-71-526-3843

ossendorp{at}mail.medfac.leidenuniv.nl

The proteasome is the principal provider of major histocompatibility complex (MHC) class I–presented peptides. Interferon (IFN)- induces expression of three catalytically active proteasome subunits (LMP2, LMP7, and MECL-1) and the proteasome-associated activator PA28. These molecules are thought to optimize the generation of MHC class I–presented peptides. However, known information on their contribution in vivo is very limited. Here, we examined the antigen processing of two murine leukemia virus-encoded cytotoxic T lymphocyte (CTL) epitopes in murine cell lines equipped with a tetracycline-controlled, IFN-–independent expression system. We thus were able to segregate the role of the immunosubunits from the role of PA28. The presence of either immunosubunits or PA28 did not alter the presentation of a subdominant murine leukemia virus (MuLV)-derived CTL epitope. However, the presentation of the immunodominant MuLV-derived epitope was markedly enhanced upon induction of each of these two sets of genes. Thus, the IFN-–inducible proteasome subunits and PA28 can independently enhance antigen presentation of some CTL epitopes. Our data show that tetracycline-regulated expression of PA28 increases CTL epitope generation without affecting the 20S proteasome composition or half-life. The differential effect of these IFN-–inducible proteins on MHC class I processing may have a decisive influence on the quality of the CTL immune response.

Key Words: antigen processing • major histocompatibility complex class I • immunoproteasomes • PA28 • murine leukemia virus

Thorbald van Hall and Alice Sijts contributed equally to this work.

© 2000 The Rockefeller University Press

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