Cell surface receptors for molecular chaperones.
Heat shock proteins are intracellular molecular chaperones. However, extracellular heat shock proteins have recently been shown to mediate a range of powerful effects in inflammatory cells, neuronal cells and immune cells. These effects are transmitted by a number of cell surface receptors including LRP/CD91, CD40, Toll-like receptors, Scavenger receptors and c-type Lectins. However, although extracellular heat shock proteins are products of at least five different gene superfamilies, similar receptor types often trigger their effects. We have assessed heat shock protein binding to the different receptor types with particular regard to its role in tumor immunology. Heat shock protein 70 released from dying tumor cells or injected as part of a vaccine induces a remarkable range of immune effects. This molecular chaperone induces powerful pro-inflammatory signaling cascades leading to the activation of antigen presenting cells. In addition, heat shock protein 70 is able to transport antigenic peptides as cargo from the tumor cell cytoplasm across the membranes of antigen presenting cells and deliver them to major histocompatability class I molecules, a process known as "cross-presentation". The resulting major histocompatability class I-peptide complexes are then displayed on the cell surface by antigen presenting cells, leading to activation of cytotoxic T lymphocytes and tumor cell killing. Understanding how heat shock protein-receptor binding orchestrates individual components of tumor immunity will permit enhanced design of molecular chaperone based immunotherapy.
Calderwood
Stuart K
SK
Molecular and Cellular Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Room 553, 21-27 Burlington Avenue, Boston, MA 02215, USA. scalderw@bidmc.harvard.edu
Theriault
Jimmy
J
Gray
Phillip J
PJ
Gong
Jianlin
J
D000818:Animals; D003593:Cytoplasm / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D037102:Lectins / Q000276:immunology / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051116:Receptors, Scavenger / Q000502:physiology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology / Q000502:physiology
D006360:Heat-Shock Proteins; D037102:Lectins; D018832:Molecular Chaperones; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D051193:Toll-Like Receptors