Abstract
A chimeric human–simian IgG, antigen specific for CD4, when exposed to 0.5 M SO=4 containing 0.4% polyethylene glycol or Jeffamine, self-assembles into discreet, roughly spherical particles 23 nm in diameter. Increasing SO=4 to 1.55 M induces the IgG particles to crystallize in either a hexagonal or a monoclinic form. From X-ray diffraction, the former crystal is of space group P622, with one IgG particle in the unit cell; thus the particle itself must have 622 point group symmetry. Both crystal forms have been imaged using atomic force microscopy. Detailed features of the duodecamer were evident, including the symmetry and a large solvent channel along the sixfold axis. The particles in some ways resemble the hexameric IgG aggregates believed to activate compliment upon antigen binding and, therefore, may have physiological relevance. Investigation of seven other IgGs of diverse origins and subclasses indicates that many, if not most, IgGs form similar particles. To our knowledge, this is the first observation of the assembly of IgG into high symmetry aggregates in the absence of antigen or their crystallization.
Highlights
The monoclonal antibody clenoliximab, designated IDEC 151, is produced by IDEC Pharmaceutical Company and has been approved for clinical use in patients with rheumatoid arthritis
The observation that the self-assembly of IgG into duodecameric particles of high symmetry occurs for a variety of monoclonal antibodies, in the presence of LiSO4 but in other salts as well, suggests that the phenomenon reported here is not highly specific, but may be general
The images of the particles are similar in some ways to the hexameric arrangement formed by IgG binding to antigen immobilized on a membrane (Uzgiris and Kornberg, 1983), as visualized by Reidler et al (1986) using electron microscopy
Summary
The monoclonal antibody clenoliximab, designated IDEC 151, is produced by IDEC Pharmaceutical Company and has been approved for clinical use in patients with rheumatoid arthritis. IDEC 151 is of isotype IgG4/ and is a primatized human immunoglobulin. The variable regions of both the heavy and light chains are derived from a monkey, while the remainders of both the light and heavy chains are of human origin (Anderson et al, 1997). The purpose of the mutations was to reduce the number of half molecules produced because of intrachain disulfide formation in the hinge between C239 and C242. This mutated antibody is known as IDEC 151 and is the molecule described here
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