Generation of antigen specific CD8+ cytotoxic T cells following immunization with soluble protein formulated with novel glycoside adjuvants.
Presentation of peptide on MHC class I molecules is essential to elicit cytolytic T cell (CTL) activity. Such peptides are a result of the cytosolic, or class I, antigen processing pathway. Due to the segregation of the class I and the exogenous processing pathway, soluble protein cannot enter the class I pathway and is thus incapable of inducing CTL. However careful formulation with adjuvants can overcome this obstacle. In this study we evaluated the capacity of two novel amphiphilic adjuvants, better termed delivery vehicles, to elicit CTL activity in a C57Bl/6 murine model with ovalbumin (OVA) as an antigen. Incomplete Freund's adjuvant and aluminium hydroxide (Alhydrogel) were used as reference adjuvants. In addition the oil-in-water emulsion Provax was used throughout as a positive control adjuvant. Both amphiphile preparations were capable of eliciting potent CTL activity after administration of one immunizing dose of ovalbumin. CTL were CD8+ restricted as assessed by in vitro depletion of CD8+ and CD4+ T cells. CTL activity was also MHC-restricted as well as specific for the H-2Kb OVA motif SIINFEKL.
Sheikh
N A
NA
Department of Immunology, St. Bartholomew's and The Royal London School of Medicine and Dentistry, UK.
Rajananthanan
P
P
Attard
G S
GS
Morrow
W J
WJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004527:Egg Proteins / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D006017:Glycolipids / Q000276:immunology / Q000494:pharmacology*; D006183:H-2 Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008070:Lipopolysaccharides / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology* / Q000494:pharmacology; D010446:Peptide Fragments; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014053:Tomatine / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D016827:CD8 Antigens; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D006017:Glycolipids; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; C110366:OVA-8; D010446:Peptide Fragments; D014053:Tomatine; D000536:Aluminum Hydroxide; D010047:Ovalbumin; D005620:Freund's Adjuvant