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*Substance via MeSH
The Journal of Immunology, 2002, 168: 4282-4286.
Copyright © 2002 by The American Association of Immunologists


Cutting Edge

Cutting Edge: CD91-Independent Cross-Presentation of GRP94(gp96)-Associated Peptides1

Brent Berwin*, Justin P. Hart{dagger}, Salvatore V. Pizzo{dagger} and Christopher V. Nicchitta2,*

Departments of * Cell Biology and {dagger} Pathology, Duke University Medical Center, Durham, NC 27710

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.




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