Heat shock proteins transfer peptides during antigen processing and CTL priming.
Recently emerging evidence indicates that the heat shock proteins (HSPs) gp96, hsp90, and hsp70 associate with antigenic peptides derived from cellular proteins. This evidence forms the basis of the following two hypotheses: 1) that HSPs constitute a relay line in which the peptides, after generation in the cytosol by the action of proteases, are transferred from one HSP to another, until they are finally accepted by MHC class I molecules in the endoplasmic reticulum, and 2) that the binding of peptides by HSPs constitutes a key step in the priming of cytotoxic T lymphocytes (CTLs) in vivo. The following chain of events is suggested: HSPs are released from virus-infected cells or tumor cells in vivo during lysis of cells during infection or by the action of antibodies or nonspecific effectors. The HSPs, which are now complexed with antigenic peptides derived from the cognate cells, are taken up by macrophage or other specialized antigen-presenting cells, possibly by a receptor-mediated mechanism. The HSP-borne peptide is then routed to the endogenous presentation pathway in the antigen-presenting cell and is displayed in the context of that cell's MHC class I, where it is finally recognized by the precursor CTLs. Thus it is suggested that, as with antigen presentation by MHC class II molecules, presentation by MHC class I molecules is also carried out primarily by the host antigen-presenting cells. This mechanism explains the phenomenon of cross-priming and has implications for the development of immunological strategies against cancer and infectious diseases.
Srivastava
P K
PK
Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029.
Udono
H
H
Blachere
N E
NE
Li
Z
Z
D000818:Animals; D017951:Antigen Presentation; D001692:Biological Transport; D006360:Heat-Shock Proteins / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006649:Histocompatibility Antigens / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000276:immunology; D010455:Peptides / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D006360:Heat-Shock Proteins; D006649:Histocompatibility Antigens; D010455:Peptides