| First Author | Murshid A | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 5 | Pages | 2903-17 |
| PubMed ID | 20686127 | Mgi Jnum | J:163244 |
| Mgi Id | MGI:4821492 | Doi | 10.4049/jimmunol.0903635 |
| Citation | Murshid A, et al. (2010) Heat shock protein 90 mediates efficient antigen cross presentation through the scavenger receptor expressed by endothelial cells-I. J Immunol 185(5):2903-17 |
| abstractText | Ag cross presentation is an important mechanism for CD8(+) T cell activation by APCs. We have investigated mechanisms involved in heat shock protein 90 (Hsp90) chaperone-mediated cross presentation of OVA-derived Ags. Hsp90-OVA peptide complexes bound to scavenger receptor expressed by endothelial cells (SREC-I) on the surface of APCs. SREC-I then mediated internalization of Hsp90-OVA polypeptide complexes through a Cdc42-regulated, dynamin-independent endocytic pathway known as the GPI-anchored protein-enriched early endosomal compartment to recycling endosomes. Peptides that did not require processing could then be loaded directly onto MHC class I in endosomes, whereas longer peptides underwent endosomal and cytosomal processing by aminopeptidases and proteases. Cross presentation of Hsp90-chaperoned peptides through this pathway to CD8(+) T cells was highly efficient compared with processing of free polypeptides. In addition, Hsp90 also activated c-Src kinase associated with SREC-I, an activity that we determined to be required for effective cross presentation. Extracellular Hsp90 can thus convey antigenic peptides through an efficient endocytosis pathway in APCs and facilitate cross presentation in a highly regulated manner. |
