Immunogenicity of a unique region of the human thyrotropin receptor.
Clarifying the role of the TSH receptor protein in the autoimmune process may be the key to understanding the development of Graves' disease. In the present study we used a 16 amino acid peptide of the human TSH receptor (hTSHR) to immunize rabbits. A comparable, but theoretically less immunogenic, peptide was injected into other rabbits. The antibody response against these and other peptides, as well as against solubilized human thyroid membrane (TM) and guinea pig fat cell membrane (GPF) proteins, was tested using ELISA and Western blots. The GPF and TM binding pattern of rabbits' sera was compared to that of Graves' patients' sera. We have identified an area of antigenic cross-reactivity between GPF and TM; a 63 kD protein was present in both GPF and TM, and this protein uniformly bound IgG-s of the rabbits' postimmunization sera and one of eight Graves' patient's serum. We have shown that i) a theoretically immunogenic 16 amino acid peptide was indeed highly immunogenic in rabbits, ii) antibodies binding to GPF and TM were detected after immunization, and iii) the peak of thyroid stimulating immunoglobulin activity of sera was followed by a transient elevation of serum triiodothyronine levels. Further studies investigating the immunogenic epitopes of the hTSHR as well as characterizing the 63 kD protein are indicated.
Nagy
E V
EV
Department of Clinical Investigation and Medicine, Walter Reed Army Medical Center, Washington, DC 20307-5001.
Burch
H B
HB
Lukes
Y G
YG
Carr
F E
FE
Kosugi
S
S
Kohn
L D
LD
Burman
K D
KD
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000235:genetics; D001323:Autoantibodies / Q000097:blood*; D003429:Cross Reactions / Q000276:immunology*; D004195:Disease Models, Animal; D006111:Graves Disease / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology*; D011817:Rabbits; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014611:Vaccination
D000906:Antibodies; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D009842:Oligopeptides; D011989:Receptors, Thyrotropin