Cell mediated immune responses against human prion protein.
Vaccination approaches that may provide protection against the abnormal form of prion protein (PrPSc) have recently focused on the ability of antibodies to prevent PrPSc propagation. Progress has been hampered due to the difficulty in generating antibody responses in wild type mice, which is believed to be a consequence of T cell tolerance to the normal form of prion protein (PrPC). The problem of tolerance can be avoided using transgenic mice unable to express PrPC. This study examines active PrP specific T cell responses that can be produced in PrP null (PrP 0/0) mice using simple peptide vaccination procedures. Spleenocytes recovered from vaccinated PrP 0/0 mice were tested in vitro for their specificity with T cell recognition demonstrated through a proliferative response to the peptide. Analysis of mRNA also indicates the stimulation of a heterogenous population of T cells with an increase in cytokines and cytotoxicity associated mRNA. Responsive T cells were expanded using a T cell cloning procedure and demonstrated an ability to recognize the mature human prion protein. These clones may potentially be used to negate the problem of T cell tolerance in wild type mice.
Bainbridge
J
J
Division of Immunobiology, NIBSC, South Mimms, UK. jbainbridge@nibsc.ac.uk
Walker
B
B
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D002999:Clone Cells; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000235:genetics / Q000276:immunology; D018620:PrPSc Proteins / Q000276:immunology*; D017096:Prion Diseases / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
D000906:Antibodies; D018621:PrPC Proteins; D018620:PrPSc Proteins; D003208:Concanavalin A; D015847:Interleukin-4