Naked deoxyribonucleic acid vaccination induces recognition of diverse thyroid peroxidase T cell epitopes.
Recently, we observed that vaccination of BALB/c mice with thyroid peroxidase (TPO)-DNA in a plasmid is highly effective at inducing antibodies that interact with the immunodominant region recognized by human autoantibodies. We have now analyzed the TPO epitopes recognized by memory T cells in these animals. Splenocytes from TPO-DNA (not control DNA)-vaccinated mice responded to TPO protein antigen, as measured by interferon-gamma production. As a group, TPO-immunized mice recognized 35 of 55 overlapping synthetic peptides that encompass the 814-amino acid TPO ectodomain. In individual mice, between five and 10 peptides induced splenocyte responses. Two T cell epitopes were immunodominant, one of which is also recognized by patients with autoimmune thyroid disease. To explore a potential correlation between T and B cell epitopes, we analyzed serum TPO antibody epitopic fingerprints. No relationship was evident. However, the number of T cell epitopes recognized by individual mice was inversely proportional to recognition of an antibody epitopic subdomain. The diversity of TPO T cell epitopes is in striking contrast to the restricted number of TSH receptor (TSHR) peptides (four of 29) recognized by T cells, as is the paucity of antibodies in the same strain of mice vaccinated with TSHR-DNA. In conclusion, our data highlight differences for both antibody and T cell epitopic recognition in TPO- vs. TSHR-DNA-immunized BALB/c mice. These findings provide insight into mechanisms that may be involved in spontaneous immune responses to two major thyroid autoantigens in humans.
Guo
Jin
J
Cedars-Sinai Medical Center, University of California School of Medicine, Los Angeles, Californoia 90048, USA.
Pichurin
Pavel N
PN
Morris
John C
JC
Rapoport
Basil
B
McLachlan
Sandra M
SM
D000595:Amino Acid Sequence; D000818:Animals; D018984:Epitopes, T-Lymphocyte; D005260:Female; D007453:Iodide Peroxidase / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D007453:Iodide Peroxidase