Ontogeny of recognition specificity and functionality for the broadly neutralizing anti-HIV antibody 4E10.

ABSTRACT: The process of antibody ontogeny typically improves affinity, on-rate, and thermostability, narrows polyspecificity, and rigidifies the combining site to the conformer optimal for binding from the broader ensemble accessible to the precursor. However, many broadly-neutralizing anti-HIV antibodies incorporate unusual structural elements and recognition specificities or properties that often lead to autoreactivity. The ontogeny of 4E10, an autoreactive antibody with unexpected combining site flexibility, was delineated through structural and biophysical comparisons of the mature antibody with multiple potential precursors. 4E10 gained affinity primarily by off-rate enhancement through a small number of mutations to a highly conserved recognition surface. Controverting the conventional paradi

SUBMITTER: Finton KA 

PROVIDER: S-EPMC4177983 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature