Abundant tyrosine residues in the antigen binding site in anti-osteosarcoma monoclonal antibodies TP-1 and TP-3: Application to radiolabeling.
The variable (V) genes of TP-1 and TP-3 MAbs have been cloned and sequenced. Because of the potential use of these antibodies in the diagnosis and treatment of osteosarcoma, it is important to determine the presence and position of amino acid residues that may react with radiolabeling within the V domains. In this article, location of the tyrosine residues is determined using the knowledge of immunoglobulin structures in general. The TP-1V domains have a total of 19 tyrosines, whereas TP-3V domains have 18, with approximately half of these located within complementarity determining regions (CDRs). Thus, if equal reactivity of all tyrosines is assumed, smaller fragments of MAbs have a high probability of being radiolabeled at one of these sites with possible resultant loss of antigen binding.
Olafsen
T
T
Division of Molecular and Cell Biology, University of Oslo, Oslo, Norway.
Bruland
O S
OS
Zalutsky
M R
MR
Sandlie
I
I
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000235:genetics / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000032:analysis* / Q000235:genetics / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D001666:Binding Sites, Antibody / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007128:Immunoglobulin Fragments / Q000032:analysis / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000235:genetics / Q000276:immunology; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000000981:diagnostic imaging / Q000276:immunology* / Q000532:radiotherapy; D011877:Radionuclide Imaging; D014443:Tyrosine / Q000032:analysis*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D007457:Iodine Radioisotopes; D014443:Tyrosine