کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2833560 1163877 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Analysis of a family of antibodies with different half-lives in mice fails to find a correlation between affinity for FcRn and serum half-life
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Analysis of a family of antibodies with different half-lives in mice fails to find a correlation between affinity for FcRn and serum half-life
چکیده انگلیسی

In this study we analyzed mouse FcRn binding to different recombinant chimeric antibodies with human constant regions. This system has the advantage that in vivo half-life in animals expressing the receptor can be directly correlated with receptor binding kinetics. The goal was to determine which FcRn binding parameters, if any, correlate with the serum half-life of antibodies. We used a BIAcore surface plasmon resonance (SPR) device to study kinetic properties at different pHs and concentrations. The data were analyzed using a new model, the dual bivalent analyte model (DBVA), which postulates that there are two types of FcRn bound to the chip, one low affinity and one high affinity. In addition, it takes into consideration the possibility that the ligand, immunoglobulin G (IgG), can exist as both monomer and as higher molecular forms. While some antibodies bind to FcRn with different kinetics, including antibodies that differ only by containing the kappa or lambda light chain – a result which itself is unexpected – we cannot identify a single FcRn binding parameter that directly correlates with Ab half-life. Importantly, we demonstrate that some IgGs with higher affinity for FcRn do not have extended in vivo half-lives.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 43, Issue 9, March 2006, Pages 1462–1473
نویسندگان
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