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gp96—The immune system's Swiss army knife

Nature Immunology volume 1, pages 100–101 (2000)Cite this article

Tumor vaccines comprised of the chaperone gp96 can instigate specific immunity to tumor peptides. A receptor on macrophages for the uptake of peptide-loaded gp96 has been identified as CD91, the α2-macroglobulin receptor.

The cellular heat shock protein gp96 is turning out to be a rather versatile molecule. It has long been known for its ability to induce immunity against antigens from the cell from which it came. For example, gp96 isolated from tumor cells induces tumor-specific immunity in animals that are intraperitoneally injected with it. Also, gp96 from the cells of BALB/c mice primes an anti–minor H cytotoxic T lymphocyte (CTL) response from C57BL/6 mice. One reason for this is the association of gp96 with peptides derived from cellular proteins. This is a strikingly specific reaction: despite the fact that other peptide-binding proteins (for example, protein disulfide isomerase) reside in the endoplasmic reticulum—the same cellular compartment that contains gp96—and that they are loaded with much larger amounts of peptides, they do not induce immunity. Thus, gp96 must possess additional features that account for its immunogenicity.

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Figure 1: Necrotic cells and apoptotic cells exert opposite effects upon antigen presenting cells.

Bob Crimi

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  1. Institute for Cell Biology Department of Immunology, University of Tübingen, Auf der Morgenstelle 15, Tübingen, D-72076, Germany

    Hansjörg Schild & Hans-Georg Rammensee

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  1. Hansjörg Schild
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  2. Hans-Georg Rammensee
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Schild, H., Rammensee, HG. gp96—The immune system's Swiss army knife. Nat Immunol 1, 100–101 (2000). https://doi.org/10.1038/77770

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