Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides.
GRP94(gp96) elicits CD8(+) T cell responses against its bound peptides, a process requiring access of its associated peptides into the MHC class I cross-presentation pathway of APCs. Entry into this pathway requires receptor-mediated endocytosis, and CD91 (low-density lipoprotein receptor-related protein) has been reported to be the receptor mediating GRP94 uptake into APC. However, a direct role for CD91 in chaperone-based peptide Ag re-presentation has not been demonstrated. We investigated the contribution of CD91 to GRP94 cell surface binding, internalization, and trafficking in APCs. Whereas a clear role for CD91 in alpha(2)-macroglobulin binding and uptake was readily obtained, the addition of excess CD91 ligand, activated alpha(2)-macroglobulin, or receptor-associated protein, an antagonist of all known CD91 ligands, did not affect GRP94 cell surface binding, receptor-mediated endocytosis, or peptide re-presentation. These data identify a CD91-independent, GRP94 internalization pathway that functions in peptide Ag re-presentation.
Berwin
Brent
B
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Hart
Justin P
JP
Pizzo
Salvatore V
SV
Nicchitta
Christopher V
CV
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D004705:Endocytosis; D026563:LDL-Receptor Related Protein-Associated Protein / Q000494:pharmacology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology; D021381:Protein Transport; D000511:alpha-Macroglobulins / Q000494:pharmacology
D000951:Antigens, Neoplasm; D026563:LDL-Receptor Related Protein-Associated Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010455:Peptides; D000511:alpha-Macroglobulins; C052646:sarcoma glycoprotein gp96 rejection antigens