Abstract
Antigen presenting cells (APCs) can take up exogenous antigenic peptides chaperoned by heat shock protein gp96 and re-present them through the endogenous pathway on their major histocompatibility class I molecules. The high efficiency of this process has been attributed previously to a receptor for gp96 on APCs. The CD91 molecule (also called α2-macroglobulin receptor or the low density lipoprotein–related protein) is shown here to be a cell surface receptor for the heat shock protein gp96. CD91 binds gp96 directly, rather than through another ligand for CD91. The previously known CD91 ligand, α2-macroglobulin, inhibits re-presentation of gp96-chaperoned antigenic peptides by macrophages, as do antibodies to CD91. As gp96 is exclusively intracellular and is released as a result of necrotic but not apoptotic cell death, we propose that CD91 acts as a sensor for necrotic cell death.
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Acknowledgements
Supported by NIH grants CA64394 and CA84479, and a research agreement with Antigenics Inc., in which P.K.S. has a significant financial interest. We thank S. Basu for sharing unpublished observations and for refining and making available the re-presentation assay, T. Matsutake, K. Anderson and R. Berlin for discussion and evaluation of experiments, and D. Ritsick for assistance with the cross-linking studies.
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Binder, R., Han, D. & Srivastava, P. CD91: a receptor for heat shock protein gp96. Nat Immunol 1, 151–155 (2000). https://doi.org/10.1038/77835
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DOI: https://doi.org/10.1038/77835
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