"Naked" deoxyribonucleic acid vaccination induces recognition of diverse thyroid peroxidase T cell epitopes

Jin Guo, Pavel N. Pichurin, John C. Morris, Basil Rapoport, Sandra M. McLachlan

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Abstract

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-γ 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-BNA-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.

Original languageEnglish (US)
Pages (from-to)3671-3678
Number of pages8
JournalEndocrinology
Volume145
Issue number8
DOIs
StatePublished - Aug 2004

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ASJC Scopus subject areas

  • Medicine(all)
  • Endocrinology

Cite this

Guo, J., Pichurin, P. N., Morris, J. C., Rapoport, B., & McLachlan, S. M. (2004). "Naked" deoxyribonucleic acid vaccination induces recognition of diverse thyroid peroxidase T cell epitopes. Endocrinology, 145(8), 3671-3678. https://doi.org/10.1210/en.2004-0303