An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response.
Heat shock protein (HSP) gp96, or grp94 is an endoplasmic reticular (ER) paralog of the cytosolic HSP90. Being abundant and non-polymorphic, gp96 plays significant roles in maintaining protein homeostasis in the secretory pathway. This "house-keeping" role of gp96 has now been overshadowed by the intriguing findings that gp96 modulates both the innate and adaptive components of the immune system. It has been found that, (i) gp96 is one of the major peptide binding proteins in the ER, (ii) gp96 interacts specifically with receptors including CD91 and possibly toll-like receptors (TLRs), on the surface of professional antigen presenting cells (APCs), (iii) interaction with APCs leads to re-presentation of gp96-chaperoned peptides to the major histocompatibility complex (MHC) molecules of APCs, (iv) direct access of gp96 to APCs triggers functional activation of APCs. In this review, we will examine each of these immunological attributes of gp96 critically. As experimentalists, we will also propose specific experiments to examine the argument that gp96, perhaps along with other members of HSP family, is the antigenic carrier for mediating cross priming of antigen-specific T lymphocytes in vertebrates.
Li
Zihai
Z
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA. zli@up.uchc.edu
Dai
Jie
J
Zheng
Hong
H
Liu
Bei
B
Caudill
Marissa
M
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000276:immunology* / Q000502:physiology; D000954:Antigens, Surface / Q000737:chemistry* / Q000276:immunology* / Q000502:physiology; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology* / Q000502:physiology
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006360:Heat-Shock Proteins; D010455:Peptides; C052646:sarcoma glycoprotein gp96 rejection antigens