Role of immunoproteasomes in cross-presentation.

Journal article

The evidence that proteasomes are involved in the processing of cross-presented proteins is indirect and based on the in vitro use of proteasome inhibitors. It remains, therefore, unclear whether cross-presentation of MHC class I peptide epitopes can occur entirely within phagolysosomes or whether it requires proteasome degradation. To address this question, we studied in vivo cross-presentation of an immunoproteasome-dependent epitope. First, we demonstrated that generation of the immunodominant HY Uty(246-254) epitope is LMP7 dependent, resulting in the lack of rejection of male LMP7-deficient (LMP7(-/-)) skin grafts by female LMP7(-/-) mice. Second, we ruled out an altered Uty(246-254)-specific T cell repertoire in LMP7(-/-) female mice and demonstrated efficient Uty(246-254) presentation by re-expressing LMP7 in male LMP7(-/-) cells. Finally, we observed that LMP7 expression significantly enhanced cross-priming of Uty(246-254)-specific T cells in vivo. The observations that male skin grafts are not rejected by LMP7(-/-) female mice and that presentation of a proteasome-dependent peptide is not efficiently rescued by alternative cross-presentation pathways provide strong evidence that proteasomes play an important role in cross-priming events.

Authors: Palmowski, M; Gileadi, U; Salio, M; Gallimore, A; Millrain, M

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 177
• Issue: 2
• Pages: 983-990
• Publication date: 2006-07-01
• DOI: 10.4049/jimmunol.177.2.983
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Mice, Knockout; Sex Factors; Proteasome Endopeptidase Complex; Male; Immunologic Surveillance; H-2 Antigens; Proteins; H-Y Antigen; Cross-Priming; Animals; Graft Rejection; Female; Cell Line, Tumor; Skin Transplantation; Mice, Inbred C57BL; Epitopes, T-Lymphocyte; T-Lymphocyte Subsets; Mice; Multienzyme Complexes