Chintalacharuvu K R, Vuong L U, Loi L A, Larrick J W, Morrison S L
Department of Microbiology, Immunology, and Molecular Genetics, Molecular Biology Institute, University of California Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095, USA.
Clin Immunol. 2001 Oct;101(1):21-31. doi: 10.1006/clim.2001.5083.
Immunoglobulin (Ig) A and IgG are the principal immune effector molecules at mucosal surfaces and in blood, respectively. Mucosal IgA is polymeric and bound to secretory component, whereas serum IgG is monomeric. We have now produced IgA2/IgG1 hybrid antibodies that combine the properties of IgA and IgG. Antibodies with Calpha3 at the end of the IgG H chain resemble IgA and form polymers with J chain that bind the polymeric Ig receptor. Like IgG, the hybrid proteins activated complement and bound FcgammaRI and protein A. Though the hybrid proteins contained both Cgamma2 and Cgamma3, they have a short in vivo half-life. Surprisingly, this decreased half-life correlated with a higher avidity than that of IgG for murine FcRn. Interestingly, antibodies with Calpha1 replacing Cgamma1 were resistant to extremes of pH, suggesting that Calpha1 increases antibody stability. These results provide insights into engineering antibodies with novel combinations of effector functions.
免疫球蛋白（Ig）A和IgG分别是黏膜表面和血液中的主要免疫效应分子。黏膜IgA是多聚体并与分泌成分结合，而血清IgG是单体。我们现已制备出结合了IgA和IgG特性的IgA2/IgG1杂交抗体。在IgG重链末端带有Cα3的抗体类似于IgA，并与J链形成聚合物，该聚合物可结合多聚免疫球蛋白受体。与IgG一样，杂交蛋白可激活补体并结合FcγRI和蛋白A。尽管杂交蛋白同时包含Cγ2和Cγ3，但它们在体内的半衰期较短。令人惊讶的是，这种缩短的半衰期与对鼠FcRn的亲和力高于IgG相关。有趣的是，用Cα1取代Cγ1的抗体对极端pH具有抗性，这表明Cα1可提高抗体稳定性。这些结果为构建具有新型效应功能组合的抗体提供了思路。
