High efficiency CD91- and LOX-1-mediated re-presentation of gp96-chaperoned peptides by MHC II molecules.
Exogenous antigens enter antigen-presenting cells through non-specific mechanisms and are presented by the MHC II molecules. We show here that antigens chaperoned by the heat shock protein gp96 enter dendritic cells and B cells through a specific, CD91- and LOX-1-mediated mechanism, and are presented by MHC II molecules, in addition to MHC I molecules as previously demonstrated. Receptor utilization results in high efficiency uptake such that antigen concentrations as low as 10(-9) M, if chaperoned by gp96, lead to productive antigen presentation. Chaperoning by gp96 increases the efficiency of uptake over un-chaperoned peptides by up to two orders of magnitude. Consistent with these studies in vitro, immunization of mice with gp96-peptide complexes (containing 5 ng peptide) results in generation of a peptide-specific CD4+ T cell response. The high efficiency suggests a mechanism in which dendritic cells, exposed in vivo to heat shock protein-chaperoned peptides liberated by virus-infected host cells or by the lysis of infecting bacteria, may prime and expand specific CD4+ responses.
Matsutake
Toyoshi
T
Department of Immunology, University of Connecticut School of Medicine, Center for Immunotherapy of Cancer and Infectious Diseases, Farmington, CT 06030-1601, USA.
Sawamura
Tatsuya
T
Srivastava
Pramod K
PK
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D051127:Scavenger Receptors, Class E / Q000276:immunology*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018832:Molecular Chaperones; C495138:Olr1 protein, mouse; D010455:Peptides; D051127:Scavenger Receptors, Class E; C052646:sarcoma glycoprotein gp96 rejection antigens