Nucleotide and amino acid homology between the human thyrotropin receptor and the HIV-1 Nef protein: identification and functional analysis.
A comparison of the nucleotide sequence of the human thyrotropin receptor (hTSH-R) with that of HIV-1 revealed 61% homology between a 161 base pair region encoding a unique portion of the hTSH-R and an immunogenic HIV-1 regulatory protein, nef. Amino acid analysis of this region shows 27% homology, including a segment in which 7/10 consecutive amino acids are identical. Sera from rabbits successfully immunized with a 16 amino acid portion of the hTSH-R (352-367, p1) was assessed for reactivity against a partially homologous nef peptide (nef-1) by ELISA, with a finding five-fold higher post-immunization values compared to pre-immune sera. The specificity of this response was verified with Western blot, using recombinant nef protein. An ELISA using nef-1 gave 64% higher values with sera from Graves' disease patients than with normal controls. This homology and immunologic cross-reactivity suggests an avenue through which a shared immune response against an HIV-1 related retrovirus could play a role in the pathogenesis of Graves' disease.
Burch
H B
HB
Department of Medicine, Walter Reed Army Medical Center, Washington, D.C. 20307-5001.
Nagy
E V
EV
Lukes
Y G
YG
Cai
W Y
WY
Wartofsky
L
L
Burman
K D
KD
D000595:Amino Acid Sequence; D000906:Antibodies; D001483:Base Sequence; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D015693:Gene Products, nef / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015754:Genes, nef; D006111:Graves Disease / Q000097:blood* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011989:Receptors, Thyrotropin / Q000235:genetics* / Q000276:immunology; D011994:Recombinant Proteins / Q000032:analysis; D012689:Sequence Homology, Nucleic Acid; D054311:nef Gene Products, Human Immunodeficiency Virus
D000906:Antibodies; D015693:Gene Products, nef; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus