Comparison of immune responses to extracellular domains of mouse and human thyrotropin receptor.
The mouse and human thyrotropin receptors show greater than 87% homology in their amino acid sequences. However, glycosylated extracellular domains of mouse (mET-gp) and human (hET-gp) thyrotropin receptors showed differences in their ability to react with patient autoantibodies to thyrotropin receptor (TSHR). To test for potential differences in their immunogenicity, we immunized BALB/c mice with either gel pure non-glycosylated ectodomain of human TSHR (ETSHR II), or hET-gp (hET-gp III), or mET-gp (mET-gp III). Alternatively, mice were primed with gel pure hET-gp or mET-gp and subsequently immunized with insect cells expressing hET-gp (hET-gp II) or mET-gp (mET-gp II) respectively. All groups of mice immunized with TSHR developed high titers of antibodies against the respective immunogens. As shown earlier, sera obtained from mice immunized with ETSHR showed strong reactivity to peptide 1 (aa 22-41) and weak reactivity to peptides 23 (aa 352-371), 24 (aa 367-386), 25 (aa 382-401), and 26 (aa 397-415). Mice immunized with hET-gp or mET-gp showed comparable titers to peptides 1 and 23 and lower reactivity to other peptides. Mice immunized with hET-gp showed higher TBII reactivity (52.2%) compared to mice immunized with either ETSHR (20.9%) or mET-gp (34.5%). Peptides from the C-terminal region of ETSHR could neutralize the TBII activities of sera from mice immunized with ETSHR or hET-gp but not mET-gp. Compared to corresponding control mice, T4 levels in mET-gp II mice were only marginally higher. These data suggested that outcome of immunization with mouse ETSHR is comparable to that seen after immunization with human ETSHR.
Patibandla
S A
SA
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Fan
J L
JL
Prabhakar
B S
BS
Seetharamaiah
G S
GS
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000276:immunology; D006111:Graves Disease; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects; D011989:Receptors, Thyrotropin / Q000276:immunology*; D013972:Thyrotropin / Q000378:metabolism; D013974:Thyroxine / Q000097:blood
D000906:Antibodies; D006023:Glycoproteins; D010446:Peptide Fragments; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D013974:Thyroxine