| First Author | Basler M | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 11 | Pages | 5548-57 |
| PubMed ID | 22013127 | Mgi Jnum | J:179599 |
| Mgi Id | MGI:5302747 | Doi | 10.4049/jimmunol.1101064 |
| Citation | Basler M, et al. (2011) The antiviral immune response in mice devoid of immunoproteasome activity. J Immunol 187(11):5548-57 |
| abstractText | The replacement of the catalytically active proteasome subunits beta1, beta2, and beta5 by the immunoproteasome subunits low molecular mass polypeptide (LMP) 2 (beta1i), multicatalytic endopeptidase complex-like-1 (MECL-1) (beta2i), and LMP7 (beta5i) is required for the production of numerous class I ligands. Hitherto, investigation of the immunoproteasome was confined to the analysis of mice deficient for one or two immunosubunits. In this study, we characterized LMP2(-/-)/MECL-1(-/-) double-deficient mice and used the well-defined LMP7-selective inhibitor ONX 0914 in these mice to generate mice lacking the activity of all immunoproteasome subunits. LMP2(-/-)/MECL-1(-/-) double-deficient mice had strongly reduced numbers of CD8(+) T cells in the spleen. Nevertheless, infection with the lymphocytic choriomeningits virus induced a normal cytotoxic T cell response in these mice, although the T cell response to several class I epitopes was altered. Treatment of LMP2(-/-)/MECL-1(-/-) double-deficient mice with the LMP7-selective inhibitor ONX 0914 elicited a strong CTL response in lymphocytic choriomeningitis virus-infected mice. Thereby, the T(CD8+) response to nucleoprotein 205-212, which is barely detectable in LMP2(-/-)/MECL-1(-/-) double-deficient mice, could be reverted to normal levels by LMP7 inhibition. Additional experiments could demonstrate that the increased CTL response to the nucleoprotein 205-212 in mice lacking functional immunoproteasome is due to an altered class I presentation of this epitope. Taken together, to our knowledge, this is the first study investigating viral infection in mice lacking activity of all three immunoproteasome subunits. |
