Chaperoning Function of Stress Protein Grp170, a Member of the Hsp70 Superfamily, is Responsible for Its Immunoadjuvant Activity.
From: Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA.
Cancer research
- Publish Date: Jan 2006
- ISSN: 0008-5472
- Volume: 66
- Issue: 2
- Pages: 1161-8
- Medium: Print
- Language: English
- Citation (JAMA): Park Jun-Eui, Facciponte John, Chen Xing, et al. Chaperoning Function of Stress Protein Grp170, a Member of the Hsp70 Superfamily, is Responsible for Its Immunoadjuvant Activity.. Cancer Res. Jan 2006;66:1161-8
Abstract
When used as vaccines, tumor-derived stress proteins can elicit antitumor immune responses. For members of the hsp70 superfamily, like grp170, this seems to be due to (a) the chaperoning of antigenic peptide by the stress protein and (b) the binding of the stress protein to receptor(s) on antigen-presenting cells (APC) and subsequent antigen presentation. This suggests that domains exist on the stress protein for each function. In this study, we determine the ability of grp170 and its structural domains to (a) bind to and present melanoma-associated antigen gp100 to the immune system and (b) to bind to receptors on APCs. A direct correlation between chaperone function, binding to APCs in a receptor-like manner, and antitumor immunity was observed. Two mutants that share no common sequence, yet are both effective in their antitumor activities, compete with one another for APC binding. Studies of other members of the hsp70 superfamily, hsp110 and hsp70, or their domain deletion mutants, further confirmed that APC binding segregates with chaperoning function and not sequence. Therefore, these studies suggest that molecular chaperoning is involved in stress protein interactions with APCs, antigen binding, and in eliciting antitumor immunity, thus bridging this ancient function of stress proteins in prokaryotes to their ability to elicit immunity in higher organisms.
Mesh Headings (Keywords): Animals, Antibody Formation, Antigen-Presenting Cells, Binding Sites, Antibody, Cancer Vaccines, Female, Glycoproteins, HSP70 Heat-Shock Proteins, Immunotherapy, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Molecular Chaperones, Neoplasm Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16424054
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.