A human Fab fragment specific for thyroid peroxidase generated by cloning thyroid lymphocyte-derived immunoglobulin genes in a bacteriophage lambda library.
A human Fab fragment (SP2) which binds specifically to human thyroid peroxidase has been generated by expressing random combinations of heavy and light chain immunoglobulin genes (derived from Graves' thyroid cDNA) in a bacteriophage lambda library. In common with many serum TPO autoantibodies, the cloned Fab fragment is IgG1 kappa and has a high affinity for TPO (approximately 10(-9) M). On the basis of their nucleotide sequences, the heavy and light chain genes coding for SP2 belong to families VHI, (D), JH3 and VKI, JK2, respectively. These data provide the first characterization at a molecular level of a human thyroid peroxidase antibody associated with autoimmune thyroid disease.
Portolano
S
S
Thyroid Molecular Biology Laboratory Unit, V. A. Medical Center, San Francisco, California 94121.
Seto
P
P
Chazenbalk
G D
GD
Nagayama
Y
Y
McLachlan
S M
SM
Rapoport
B
B
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000235:genetics*; D010582:Bacteriophage lambda / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular / Q000379:methods*; D015723:Gene Library; D005803:Genes, Immunoglobulin; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics* / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007453:Iodide Peroxidase / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013961:Thyroid Gland / Q000201:enzymology / Q000276:immunology*
D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D011994:Recombinant Proteins; D007453:Iodide Peroxidase