title: Adjuvant potential of aggregate-forming polyglutamine domains.
abstract: Aggregation may significantly affect the fate of a polypeptide, including its susceptibility to proteasome-dependent or autophagic degradation, its interaction with chaperones, etc. Since all these factors may affect the antigenicity of a polypeptide, we hypothesized that stimulating aggregation of an antigenic protein by its fusion to polyQ domain may enhance its antigenic potential. This hypothesis was tested with the weakly immunogenic model antigen GFP, which was fused to either long polyQ domain that triggers protein aggregation (103Q), or short polyQ domain that does not promote aggregation (25Q). Plasmids encoding control pGFP or soluble 25Q-GFP generated a very weak antibody response, while a significant increase in anti-GFP antibody titer was seen in groups immunized with DNA encoding aggregating 103Q-GFP. Similarly, fusion with 103Q strongly enhanced anti-GFP CTL activity, compared to fusion with 25Q. No apparent toxicity was observed after immunization with polyQ-GFP fusions. These data suggest that fusion of an antigen with expanded polyQ domains could have a significant adjuvant potential.
authors.affiliation: Cure Lab Inc, Canton, MA 02021, USA.
authors.forename: P O
authors.initials: PO
authors.lastname: Ilyinskii
authors.forename: G
authors.initials: G
authors.lastname: Thoidis
authors.forename: M Y
authors.initials: MY
authors.lastname: Sherman
authors.forename: A
authors.initials: A
authors.lastname: Shneider
mesh_terms: D000276:Adjuvants, Immunologic; D000906:Antibodies / Q000097:blood; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D007155:Immunologic Factors; D010455:Peptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C097188:polyglutamine