Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Berwin, B; Hart, JP; Pizzo, SV; Nicchitta, CV

Published Date

  • May 1, 2002

Published In

Volume / Issue

  • 168 / 9

Start / End Page

  • 4282 - 4286

PubMed ID

  • 11970968

Pubmed Central ID

  • 11970968

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.168.9.4282


  • eng

Conference Location

  • United States