TY - JOUR
T1 - "Naked" deoxyribonucleic acid vaccination induces recognition of diverse thyroid peroxidase T cell epitopes
AU - Guo, Jin
AU - Pichurin, Pavel N.
AU - Morris, John C.
AU - Rapoport, Basil
AU - McLachlan, Sandra M.
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
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U2 - 10.1210/en.2004-0303
DO - 10.1210/en.2004-0303
M3 - Article
C2 - 15123538
AN - SCOPUS:3843141619
SN - 0013-7227
VL - 145
SP - 3671
EP - 3678
JO - Endocrinology
JF - Endocrinology
IS - 8
ER -