The N-terminal fragment of GRP94 is sufficient for peptide presentation via professional antigen-presenting cells.
The chaperone glucose-regulated protein 94 (GRP94) has long been used to augment peptide presentation to T cells. This chaperone binds antigenic peptides, binds to receptors on professional antigen-presenting cells (APCs), activates these cells and after internalization, transfers the peptides to MHC class I for activation of T cells. Here we show that all these activities reside within amino acids 1-355 of GRP94. This small fragment is sufficient to bind peptides, to bind and be taken up by the receptors CD91 and scavenger receptor type A on either dendritic cells or macrophages. The minimal construct can augment peptide presentation in culture and induce antigen-specific CTL in naive mice only because it loads APCs with the relevant peptide. Thus, the sequence 1-355 is the immunologically sufficient module of GRP94 and we propose that this 'mini-chaperone' can be used in immunotherapy of tumors and vaccine development.
Biswas
Chhanda
C
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA.
Sriram
Uma
U
Ciric
Bogoljub
B
Ostrovsky
Olga
O
Gallucci
Stefania
S
Argon
Yair
Y
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010455:Peptides / Q000276:immunology*; D011973:Receptors, LDL; D051117:Scavenger Receptors, Class A / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D025521:Tumor Suppressor Proteins; D014612:Vaccines / Q000276:immunology
D015703:Antigens, CD; D006360:Heat-Shock Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D011973:Receptors, LDL; D051117:Scavenger Receptors, Class A; D025521:Tumor Suppressor Proteins; D014612:Vaccines; C053387:endoplasmin