| First Author | Oliveira CC | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 8 | Pages | 4020-8 |
| PubMed ID | 24048903 | Mgi Jnum | J:206256 |
| Mgi Id | MGI:5548271 | Doi | 10.4049/jimmunol.1301496 |
| Citation | Oliveira CC, et al. (2013) New role of signal peptide peptidase to liberate C-terminal peptides for MHC class I presentation. J Immunol 191(8):4020-8 |
| abstractText | The signal peptide peptidase (SPP) is an intramembrane cleaving aspartyl protease involved in release of leader peptide remnants from the endoplasmic reticulum membrane, hence its name. We now found a new activity of SPP that mediates liberation of C-terminal peptides. In our search for novel proteolytic enzymes involved in MHC class I (MHC-I) presentation, we found that SPP generates the C-terminal peptide-epitope of a ceramide synthase. The display of this immunogenic peptide-MHC-I complex at the cell surface was independent of conventional processing components like proteasome and peptide transporter TAP. Absence of TAP activity even increased the MHC-I presentation of this Ag. Mutagenesis studies revealed the crucial role of the C-terminal location of the epitope and "helix-breaking" residues in the transmembrane region just upstream of the peptide, indicating that SPP directly liberated the minimal 9-mer peptide. Moreover, silencing of SPP and its family member SPPL2a led to a general reduction of surface peptide-MHC-I complexes, underlining the involvement of these enzymes in Ag processing and presentation. |
