| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
The IgG antibody contains variable ligands binding sites to perform immunological functions on its protein molecule. These are two binding regions to antigen and protein L on Fab portion, one Fc gamma receptor binding region on near hinge region, and two binding regions to the neonatal Fc receptor (FcRn), C lq or bacterial proteins like protein A and protein G on Fc portion. More recently, Fc portion of IgG as non antibody binding site was focused to play an important role in regulating the serum half-lives of IgG antibodies. In this study, in order to establish therapeutic and immunoassay with authentic antibodies to abnormal prion and dioxin, molecular modeling and peptide array were used to identify IgG binding site in a human FcRn that, when mutated, might alter the binding affinity of FcRn to IgG. FITC labeled monoclonal human IgG1 bound to four domains, A, B, C, and D of human FcRn peptide array on cellulose membrane. Domain A of FcRn was predicted to bind to the CH2/CH3 interface based on 3D structure of rat IgG/FcRn complex as well as protein A binding site. FITC labeled protein A as probe, and the peptide array of exhaustive mutated CH2/CH3 interface region could be used to find the strongest binding peptide sequences to protein A. Also, peptide array and FITC labeled peptide probe mutated peptides of FcRn domain A may be useful to discover the longest half-lives authentic antibody contained antigen binding domain as new antibody engineering technology.
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